Haiquan Chen

Fudan University, Shanghai, Shanghai Shi, China

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Publications (113)633.64 Total impact

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    ABSTRACT: Our aim was to investigate the clinical and pathologic characteristics of the epidermal growth factor receptor (EGFR) exon 18 mutations in East Asian lung adenocarcinomas patients. A total of 1,201 lung adenocarcinomas were analyzed for mutation in EGFR. Clinical and pathologic characteristics of patients with EGFR exon 18 mutations were compared with those who harbored classic activating mutations (exon 19 deletions and the L858R point mutation). The mutations in EGFR exon 18 were observed in 2.8% of 1,201 lung adenocarcinomas and 4.6% of patients with EGFR mutations. Patients with a single EGFR exon of 18 mutations had a worse overall survival than those harboring the complex EGFR exon of 18 mutations (p = 0.002) or those with classic activating mutations (p = 0.014). Four of five patients with EGFR exon 18 mutations showed objective response to the EGFR-TKI therapies after disease recurrence. Our results demonstrated that single EGFR exon 18 mutations may be an indicator of poor prognosis compared with complex EGFR exon 18 mutations or classic mutations. Furthermore, the results of the current study will be helpful for decision-making in the treatment of patients with EGFR exon 18 mutations.
    Scientific Reports 09/2015; 5:13959. DOI:10.1038/srep13959 · 5.58 Impact Factor
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    ABSTRACT: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC). Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS). p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival. Activation of AKT1 was associated with poor prognosis in ESCC.
    Journal of Experimental & Clinical Cancer Research 09/2015; 34(1):95. DOI:10.1186/s13046-015-0212-z · 4.43 Impact Factor
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    ABSTRACT: Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.
    Scientific Reports 08/2015; · 5.58 Impact Factor
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    ABSTRACT: This study was designed to identify the prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma, and to reveal the association between BRAF mutations and clinicopathological characteristics in these patients. From October 2007 to February 2013, patients with newly diagnosed primary lung adenocarcinoma were detected for mutations in BRAF, EGFR, KRAS, HER2 and ALK. Clinicopathological characteristics, including sex, age, TNM stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed. Of 1358 patients with lung adenocarcinoma, 20 patients were harboring BRAF mutations, including five BRAF V600E mutations and 15 BRAF non-V600E mutations. Among these, BRAF N581I and BRAF G593S were newly reported. BRAF mutations were associated with smoking status (odds ratio 3.28; 95 % CI 1.33-8.08; p = 0.008). In patients less than 60 years of age, BRAF mutations tended to have poor differentiation in tumor samples (70.0 vs. 35.1 %; p = 0.014), and were more likely to relapse (70 vs. 28 %; p = 0.008). A significant difference was found in relapse-free survival (RFS) between BRAF mutations and other mutations, but not in overall survival. The prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma was approximately 1.5 %. BRAF mutations were more frequent in current smokers. Patients harboring BRAF mutations had a higher rate of recurrence and worse RFS compared with other patients.
    Annals of Surgical Oncology 07/2015; DOI:10.1245/s10434-015-4640-y · 3.93 Impact Factor
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    ABSTRACT: Thyroid transcription factor 1 (TTF1) is a master regulator of pulmonary differentiation that is downregulated in a subset of lung adenocarcinoma, of which the clinicopathologic characteristics were not fully clarified. One thousand forty-two lung adenocarcinoma patients who underwent surgery were investigated for clinic characteristics, histologic subtyping, and spectrum of well-identified driver mutations. TTF1 expression was correlated with these clinicopathologic factors and survival. Compared with TTF1 positive (TTF1+) patients, the 133 negative individuals (12.8%, TTF1-) were more likely to be male (p = 0.006) and heavy smokers (p = 0.002) who had larger tumor size (p < 0.001) and more advanced disease stage (p < 0.001). TTF1- presented more in solid and invasive mucinous-predominant carcinomas (both p < 0.001), whereas TTF1+ was identified in 100% patients with adenocarcinoma in situ, minimally invasive and lepidic-predominant adenocarcinomas. The TTF1- tumors harbored the known driver mutations in significantly low frequency compared with TTF1+ adenocarcinomas (57.8% versus 78.1%, p < 0.001), especially in epidermal growth factor receptor (EGFR) mutations (37.6% versus 60.7%, p < 0.001). There was no significant difference in recurrence-free survival between the TTF1- and TTF1+ patients, either for the whole cohort or stratified by pathologic stage, or among the driver mutation-defined subsets. However, recurrence of multiple metastases was more likely to occur in patients with TTF1- adenocarcinomas (88.1% versus 32.4%, p < 0.001). Multivariate analysis revealed that TTF1- -independently predicted both poor postrecurrence survival (hazard ratio = 1.664; 95% confidence interval , 1.097-2.524; p = 0.017) and unfavorable overall survival (hazard ratio = 1.553; 95% confidence interval , 1.013-2.381; p = 0.043). TTF1- correlated with solid and invasive mucinous subtypes of lung adenocarcinoma and lower frequency of EGFR mutations. It defines a subgroup of lung adenocarcinomas with unfavorable outcomes.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2015; DOI:10.1097/JTO.0000000000000626 · 5.28 Impact Factor
  • Hang Li · Hong Hu · Rui Wang · Yuan Li · Lei Shen · Yihua Sun · Haiquan Chen
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    ABSTRACT: This study investigated the association between clinical pathologic features, especially adenocarcinoma subtypes and prognosis, and skip N2 metastasis in patients with lung adenocarcinoma. In this study, 177 patients with lung adenocarcinoma and N2 metastasis were enrolled. Patients who had N2 lymph node metastases without N1 lymph node involvement were defined as skip N2 and otherwise as non-skip N2. We investigated the difference of clinicopathologic characteristics, recurrence-free survival, overall survival, and spectrum of well-identified molecular alterations in EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET genes in the 2 groups. Skip N2 metastasis was found in 45 patients, in whom a remarkably lower incidence of lymphovascular invasion was revealed (P = .01). Skip N2 metastasis was also associated with acinar subtype, good differentiation, and right lung cancer. The recurrence-free survival and overall survival were significantly better in the skip N2 group (5-year recurrence-free survival 37.4% vs 5.7%; log-rank P = .005; 5-year overall survival 60.7% vs 32.1%; log-rank P = .024). The predictive value of skip N2 was more significant in patients with lesions in the right lung (5-year recurrence-free survival 36.6% vs 0.0%; log-rank P = .002; 5-year overall survival 57.2% vs 27.9%; log-rank P = .016) and in patients whose tumor diameter was no more than 3 cm (5-year recurrence-free survival 43.1% vs 6.7%; log-rank P = .01; 5-year overall survival 74.6 vs 27.6%; log-rank P = .04). There are distinct differences in clinicopathologic features and prognosis in patients with or without skip N2 metastasis. Considering the results of our study, subclassifications of mediastinal lymph node metastases could have clinical significance for patients with lung adenocarcinoma. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    The Journal of thoracic and cardiovascular surgery 07/2015; DOI:10.1016/j.jtcvs.2015.03.067 · 4.17 Impact Factor
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    Bin Pan · Rui Wang · Yangle Huang · David Garfield · Jie Zhang · Haiquan Chen
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    ABSTRACT: Although over-expression of hepatocyte growth factor (HGF) and neuregulin-1 (NRG1) are important mechanisms involved in acquired drug-resistance in many cancers, few reports have evaluated their clinicopathologic features and prognostic significance. The aim of our study was to investigate protein expressions of HGF and NRG1 in lung adenocarcinomas and their association with clinicopathologic parameters, oncogenic mutations, and the prognosis. HGF and NRG1 protein tumor/stroma expressions were evaluated by immunohistochemistry (IHC) in 115 surgically resected lung adenocarcinomas and were correlated with clinicopathologic and molecular variables including tumor size, tumor node metastasis stage, differentiation, oncogenic mutations (EGFR, KRAS, HER2, BRAF) and ALK fusions, relapse-free survival, and overall survival. Positive IHC HGF tumor and stroma staining were found in 49 (42.61%) and 12 (10.43%) cases, respectively, while positive IHC NRG1 tumor and stroma staining were found in 56 (48.70%) and eleven (9.57%) cases, respectively. Dual positive IHC HGF and NRG1 tumor staining was 12.17%. EML4-ALK fusion more significantly existed in HGF-tumor positive samples (P=0.03), positive NRG1 protein stroma expression was significantly associated with male sex (P=0.04), while HGF and NRG1 dual tumor-positive mainly existed in the tumor size >3 cm group (P=0.0231). No significant clinically prognostic difference was found between patients with HGF/NRG1-positive expression and those with HGF/NRG1-negative expression. This study represents the first comprehensive analysis of HGF and NRG1 tumor and stroma expressions in patients with surgically resected lung adenocarcinomas. Our molecular data, in conjunction with clinical and pathological features, as well as their effects on survival indicated to us that patients with HGF- and NRG1-negative expression tended to have better survival, but these results probably did not warrant these markers to be indicators of poor prognosis.
    OncoTargets and Therapy 05/2015; 8:1185-91. DOI:10.2147/OTT.S78116 · 2.31 Impact Factor
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    ABSTRACT: LKB1 regulates both cell growth and energy metabolism. It remains unclear how LKB1 inactivation coordinates tumor progression with metabolic adaptation in non-small cell lung cancer (NSCLC). Here in Kras(G12D);Lkb1(lox/lox) (KL) mouse model, we reveal differential reactive oxygen species (ROS) levels in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). ROS can modulate ADC-to-SCC transdifferentiation (AST). Further, pentose phosphate pathway deregulation and impaired fatty acid oxidation collectively contribute to the redox imbalance and functionally affect AST. Similar tumor and redox heterogeneity also exist in human NSCLC with LKB1 inactivation. In preclinical trials toward metabolic stress, certain KL ADC can develop drug resistance through squamous transdifferentiation. This study uncovers critical redox control of tumor plasticity that may affect therapeutic response in NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cancer cell 04/2015; 27(5). DOI:10.1016/j.ccell.2015.04.001 · 23.52 Impact Factor
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    ABSTRACT: Background Chylothorax is a rare but serious postoperative complication in esophageal cancer patients. The aim of this study was to identify risk factors associated with chylothorax and the indication for surgical intervention.MethodsA consecutive series of 1290 patients who underwent esophagectomy for esophageal cancer was included. Peri-operative data, including postoperative morbidity and mortality, were analyzed.ResultsThirty-four patients (2.6%) developed chylothorax and had significantly higher instances of pneumonia (26.5% vs. 11.1%, P = 0.012) and arrhythmia (17.6% vs. 2.9%, P = 0.001), and a longer hospital stay (22 vs. 18 days, P < 0.001). Reoperation was performed in 11 patients at a rate of 77.8%, 42.9%, 20%, and 0% for chylothorax diagnosed in two, three, four, and >= 5 days, respectively, after esophagectomy (P < 0.001). After three days of conservative therapy, the chest tube output was significantly greater in patients whose medical management had failed than in those successfully treated (P < 0.001). All patients who required reoperation had >= 13.5 ml/kg of drainage (sensitivity 100%); four of 23 patients with successful medical management had a chest tube output >= 13.5 ml/kg (specificity 83%). Logistic regression analysis showed that body mass index (BMI) < 25 was an independent risk factor for chylothorax (hazard ratio = 9.256, P = 0.029).Conclusions Patients with a BMI < 25 are more likely to develop chylothorax after esophagectomy. Operative therapy should be seriously considered in patients who develop chylothorax early postoperatively. In addition, a high daily chylous output of >= 13.5 ml/kg after three days of conservative therapy might be a reliable indicator for reoperation.
    Thoracic Cancer 03/2015; 6(3). DOI:10.1111/1759-7714.12240 · 0.90 Impact Factor
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    ABSTRACT: Sweet esophagectomy is performed widely in China, while the Ivor-Lewis procedure, with potential benefit of an extended lymphadenectomy, is limitedly conducted owing to concern for a higher risk for morbidity. Thus, the role of the Ivor-Lewis procedure for thoracic esophageal cancer needs further investigation. To determine whether Ivor-Lewis esophagectomy is associated with increased postoperative complications compared with the Sweet procedure. A randomized clinical trial was conducted from May 2010 to July 2012 at Fudan University Shanghai Cancer Center, Shanghai, China, of 300 patients with resectable squamous cell carcinoma in the middle and lower third of the thoracic esophagus. Intent-to-treat analysis was performed. Patients were randomly assigned to receive either the Ivor-Lewis (n = 150) or Sweet (n = 150) esophagectomy. The primary outcome of this clinical trial was operative morbidity (any surgical or nonsurgical complications). Secondary outcomes included oncologic efficacy (number of lymph nodes resected and positive lymph nodes), postoperative mortality (30-day and in-hospital mortality), and patient discharge. Resection without macroscopical residual (R0/R1) was achieved in 149 of 150 patients in each group. Although there was no significant difference between the 2 groups regarding the incidence of each single complication, a significantly higher morbidity rate was found in the Sweet group (62 of 150 [41.3%]) than in the Ivor-Lewis group (45 of 150 [30%]) (P = .04). More patients in the Sweet group (8 of 150 [5.3%]) received reoperations than in the Ivor-Lewis group (1 of 150 [0.7%]) (P = .04). The median hospital stay was 18 days in the Sweet group vs 16 days in the Ivor-Lewis group (P = .002). Postoperative mortality rates in the Ivor-Lewis (1 of 150) and Sweet (3 of 150) groups were 0.7% and 2.0%, respectively (P = .25). More lymph nodes were removed during Ivor-Lewis esophagectomy than during the Sweet procedure (22 vs 18, P < .001). Early results of this study demonstrate that the Ivor-Lewis procedure can be performed with lower rates of postoperative complications and more lymph node retrieval. Ivor-Lewis and Sweet esophagectomies are both safe procedures with low operative mortalities. clinicaltrials.gov Identifier:NCT01047111.
    02/2015; 150(4). DOI:10.1001/jamasurg.2014.2877
  • Yang Zhao · Haiquan Chen · Jianxin Shi · Limin Fan · Dingzhong Hu · Heng Zhao
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    ABSTRACT: Chest computed tomography (CT) scanning has been widely utilized in thymoma identification and staging as well as in follow-up monitoring for recurrence. However, the relationship between some CT imaging features and pathological types, clinical stage, completeness of resection, or prognosis in thymoma has not been well explored. We retrospectively reviewed preoperative CT imaging for 238 thymoma patients, who had undergone thymectomy from October 2007 to December 2011. All CT parameters were assessed in each case based on clinical and pathological data. Survival analysis was performed by using the Kaplan-Meier and log-rank tests. Tumour contours (P = 0.008), homogeneity (P = 0.009), degree of enhancement (P = 0.013), fat plane obliteration with adjacent structures (P < 0.001), the presence of mediastinal lymphadenopathy (P = 0.010), irregular infiltration into the lung (P = 0.012) and tumour shape (P = 0.007) were associated with the World Health Organization (WHO) histological classification. Lobulated or irregular tumour contours (P < 0.001), presence of calcifications (P = 0.002), infiltration of surrounding fat (P < 0.001), irregular infiltration into the lung (P < 0.001), irregular infiltration into vascular (P < 0.001), more abutment of vessels (P < 0.001) and pulmonary changes adjacent to the tumour (P < 0.001) were associated with the more advanced Masaoka-Koga clinical stage. Tumour contours (P < 0.001), infiltration of surrounding fat (P = 0.008), irregular infiltration into the lung (P < 0.001) and degree of abutment of vessel circumference (P = 0.001) were associated with completeness of resection. With multivariate analysis, no CT image features could reliably predict on the overall or disease-free survival rate. CT imaging does have some features, which are significantly correlated with the WHO classification, the Masaoka-Koga clinical staging and the completeness of resection, although it has no definite role to evaluate preoperatively the survival rate of thymoma patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2014; DOI:10.1093/ejcts/ezu475 · 3.30 Impact Factor
  • Longsheng Miao · Haiquan Chen · Jiaqing Xiang · Yawei Zhang
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    ABSTRACT: There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients. From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI ≥ 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models. The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors. A high BMI is not associated with increased overall morbidity following esophagectomy; moreover, it is associated with decreased incidence of chylothorax. The better overall survival in patients with high BMI compared with those with low BMI might be due to a relatively low pathological stage. A high BMI should therefore not be a relative contraindication for esophagectomy.
    Journal of Cancer Research and Clinical Oncology 11/2014; 141(5). DOI:10.1007/s00432-014-1878-x · 3.08 Impact Factor
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    ABSTRACT: A total of 1039 stage I-III invasive lung adenocarcinoma including 186 solid subtype patients who have undergone radical resection were assessed for clincopathlogic characteristics, status of common driver mutations, pattern of recurrence, recurrence-free survival (RFS), overall survival (OS), post-recurrence survival (PRS) and predictive value for adjuvant chemotherapy and EGFR tyrosine kinase inhibitors (TKIs). Solid predominant adenocarcinomas were more likely to have initial distant recurrences than non-solid subtype invasive adenocarcinomas (P = 0.018). In univariate analysis, solid predominant adenocarcinoma patients had significantly worse RFS (P < 0.001), OS (P < 0.001) and PRS (P = 0.010). Multivariate analysis adjusting for clinicopathologic variables and mutational status showed that solid subtype was an independent poor prognostic factor (odds ratio = 1.876, 95% confidence interval: 1.291-3.158; P = 0.003) and an independent negative predictor for stage II-III patients undergoing adjuvant chemotherapy (odds ratio = 2.020, 95% confidence interval: 1.291-3.158; P = 0.002). In EGFR-mutated solid predominant lung adenocarcinoma patients who experienced disease recurrence, the response rate to EGFR TKIs was only 37.5%. In radically resected invasive lung adenocarcinoma, solid subtype was an independent poor prognostic factor and negative predictor for adjuvant chemotherapy.
    Scientific Reports 11/2014; 4:7163. DOI:10.1038/srep07163 · 5.58 Impact Factor
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    ABSTRACT: We performed this analysis to distinguish the differences in two subtypes of lung invasive mucinous adenocarcinoma (IMA) with different kinds of morphological performances, in clinicopathological and molecular features, as well as prognosis. On the basis of morphological performance, we divided lung IMAs into two subgroups, mucus-in-cell adenocarcinoma (MICA) and mucus-out-of-cell adenocarcinoma (MOCA). We investigated differences in clinicopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and a spectrum of well-identified driver-gene mutations, including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET, between the two subgroups. Of 1,699 lung adenocarcinomas, 148 were identified as IMAs (97 MICAs and 51 MOCAs). The MICA patient group had significantly better RFS than did the MOCA group (39.4 months versus 33.0 months, respectively, log rank P=0.020) and significantly better OS (54.2 months versus 45.1 months, log rank P=0.034). There were no differences in RFS and OS between those with IMAs and those with mucus-negative adenocarcinomas. The frequency of the EGFR gene mutation was significantly higher in MOCAs than in MICAs (P<0.001). In contrast, the KRAS gene had a significantly higher mutational frequency in MICAs (P=0.01). MOCAs also had a significantly higher incidence of lymph-node metastasis (P<0.05). To our knowledge, this study represents the first comparison of clinical features, molecular alterations, and prognosis in morphological subgroups of lung IMAs. Clinical and pathological features in conjunction with molecular data indicate that IMA should be divided into different subgroups.
    OncoTargets and Therapy 11/2014; 7:2127-2132. DOI:10.2147/OTT.S70984 · 2.31 Impact Factor
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    ABSTRACT: Introduction The recurrent TERT promoter mutations have been recently described in diverse human cancers. We previously showed that over 60% of non-small cell lung cancer from East Asian harbored well-known oncogenic mutations in EGFR and KRAS. Here, we sought to determine the incidence, clinicopathologic characteristics, and association with known oncogenic mutations. Patients and Methods A total of 467 patients treated surgically for primary lung cancer were examined for mutations in TERT promoter using polymerase chain reaction (PCR) followed by Sanger sequencing. Immunohistochemical (IHC) staining was performed to detect the expression of TERT. Clinical characteristics including gender, age, smoking status, tumor size, differentiation, lymph node metastasis, TNM stage, overall survival and relapse-free survival were analyzed. Results Of 467 patients with non-small cell lung cancer, the TERT promoter mutation was detected in 12 patients. Of the 12 patients, 3 with C228 T, 2 with C250 T, 2 with C216 T, 1 with C228A, 1 with C229G, 1 with G267 C, 1 with C295 T and 1 with G233 C. Compared to the TERT mutation negative group, patients with TERT promoter mutation were significantly associated with older age (≥60 years, P = 0.039). No significant difference was found in overall survival (OS) or relapse-free survival (RFS) between TERT with mutation and TERT without mutation. Conclusions TERT promoter mutations are recurrent mutated in 2.57% of NSCLCs and are highly enriched in older patients. It may play an important role in the pathogenesis of NSCLC and may serve as a potential target for therapy.
    Lung Cancer 10/2014; 86(3). DOI:10.1016/j.lungcan.2014.10.009 · 3.96 Impact Factor
  • Yang Zhang · Yihua Sun · Rui Wang · Ting Ye · Yiliang Zhang · Haiquan Chen
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    ABSTRACT: Background Survival difference following lobectomy, segmentectomy, and wedge resection in stage I non-small cell lung cancer (NSCLC) and its subgroups remains undetermined.Methods We systemically searched published articles comparing recurrence-free survival (RFS), overall survival (OS), or cancer-specific survival (CSS) between lobectomy and limited resection or between segmentectomy and wedge resection.ResultsA total of 42 studies published from 1980 to 2014 enrolling 21,926 patients were included in this meta-analysis. Survival results favored lobectomy in stage IA NSCLC ≤2 cm (combined HR: 1.530, 95% CI: 1.402–1.671, P < 0.001) or patient's ≥65 years old (combined HR: 1.227, 95% CI: 1.003–1.502, P = 0.047). Survival outcome of video-assisted thoracoscopic (VATS) sublobectomy was comparable to that of VATS lobectomy (pooled HR: 0.808, 95% CI: 0.556–1.174, P = 0.263). The combined HR of segmentectomy versus lobectomy was 1.231 (95% CI: 1.070–1.417, P = 0.004), while the pooled HR of wedge resection versus segmentectomy was 1.542 (95% CI: 0.856–2.780, P = 0.149).Conclusions This study suggested that tumor size or age alone should not be the criteria to encourage sublobar resection. For stage I NSCLC, survival following segmentectomy was inferior to lobectomy. Patients undergoing intentional sublobectomy achieved comparable survival as those who received lobectomy. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 10/2014; 111(3). DOI:10.1002/jso.23800 · 3.24 Impact Factor
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    ABSTRACT: Introduction: The youthful lung cancer may constitute an entity with distinct clinicopathologic characteristics and a controversial prognosis compared with the older counterpart. Whether the youthful lung cancer has the exclusively distinct molecular features has not been well investigated. Methods: Thirty-six resected lung adenocarcinomas from young patients under 40 years old were analyzed concurrently for mutations in EGFR, KRAS, HER2, BRAF, AKT1, ALK, RET, TP53 and LKB1 and enrolled as the younger group. Their molecular and clinicopathologic characteristics were compared with those of 87 adenocarcinoma cases from patients above 40 years old which were collected as the older group. Results: The comparable overall survival (OS) (P=0.942), more early adenocarcinomas (P=0.033), more wedge resections (P<0.001) and fewer smokers (P=0.004) were seen in the younger group, when compared with the clinicopathologic characteristics in the older group. Nineteen EGFR mutations (52.8%), 3 KRAS mutations (8.3%), 2 EML4-ALK fusions (5.6%) and 1 KIF5b-RET fusion (2.8%) were identified in the younger group. The difference of oncogenic mutations between the two groups was statistically insignificant (P=0.396). Twenty-six TP53 mutations (72.2%) and 4 LKB1 mutations (11.1%) were found in the younger group. When compared with the old patients, young patients showed a higher prevalence of TP53 mutations (P<0.001) and a comparable prevalence of LKB1 mutations (P=0.951). Conclusions: The youthful lung cancer unequivocally presented the distinct clinicopathologic characteristics including more early adenocarcinomas and fewer smokers. It showed the similar oncogenic characteristics and higher prevalence of TP53 mutations compared with the older counterpart.
    Journal of Thoracic Disease 10/2014; 6(10):1396-402. DOI:10.3978/j.issn.2072-1439.2014.08.50 · 1.78 Impact Factor
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    Xinghua Cheng · Haiquan Chen
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    ABSTRACT: Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed.
    OncoTargets and Therapy 09/2014; 7:1689-704. DOI:10.2147/OTT.S66502 · 2.31 Impact Factor
  • Hang Li · Yunjian Pan · Rui Wang · Yuan Li · Yihua Sun · Haiquan Chen
    Journal of Cancer Research and Clinical Oncology 09/2014; 141(1). DOI:10.1007/s00432-014-1821-1 · 3.08 Impact Factor
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    ABSTRACT: Introduction: Both micropapillary predominant lung adenocarcinoma according to the IASLC/ATS/ERS classification and lung adenocarcinoma with a micropapillary component have been reported to be associated with poor prognosis. However, whether they have different prognosis remains undetermined. Methods: Out of 1302 lung adenocarcinoma patients, 21 patients with micropapillary predominant lung adenocarcinoma (MPP) and 100 patients with nonmicropapillary predominant tumors harboring a micropapillary component of at least 5% (MPC) were investigated for clinicopathologic characteristics, recurrence-free survival (RFS), overall survival (OS), and spectrum of well-identified driver mutations including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET. Results: Twenty out of 21 (95.2%) micropapillary predominant lung adenocarcinoma harbored driver mutations in EGFR (85.7%), HER2 (4.8%), or RET (4.8%). MPP had significantly worse RFS than MPC in stage I patients (p = 0.003), but not in stages II-III patients. The overall survival was comparable between MPP and MPC regardless of disease stages. Objective response was achieved in 13 out of the 18 MPP or MPC patients with EGFR mutations who received EGFR tyrosine kinase inhibitors (TKIs) after disease recurrence. The postrecurrence survival was significantly better in EGFR-mutated patients who were treated with EGFR TKIs compared to those who did not receive TKIs (p = 0.003). Conclusions: Micropapillary predominant lung adenocarcinoma is a disease that could be largely defined by targetable driver mutations. For stage I lung adenocarcinoma, MPP was even more likely to recur than MPC. EGFR TKIs might help to control the recurrent disease for MPP or MPC patients harboring EGFR mutations.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2014; 9(12). DOI:10.1097/JTO.0000000000000341 · 5.28 Impact Factor

Publication Stats

2k Citations
633.64 Total Impact Points


  • 2009–2015
    • Fudan University
      • Department of Oncology
      Shanghai, Shanghai Shi, China
  • 2013
    • Vanderbilt University
      • Department of Biomedical Informatics
      Нашвилл, Michigan, United States
  • 2012
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2010
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China