Haiquan Chen

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai Shi, China

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Publications (127)700.03 Total impact

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    ABSTRACT: Background Lung adenocarcinoma with micropapillary and solid predominant subtypes was reported to be associated with poor prognosis; however, whether minor components (non-predominant) of micropapillary and solid subtypes predict poor prognosis remains unknown. In this study, we investigated the predictive and prognostic value of lymph node metastasis of minor micropapillary and solid components. Methods Specimens of resected tumors of 1244 patients were reclassified to determine the predominant subtype and minor components (>5 %, but not predominant). Of these specimens, 105 contained a micropapillary component and 210 contained a solid component. The correlation between each subtype and lymph node metastasis was analyzed, and survival analyses were used to determine the association between each subtype and patient survival. Results Adenocarcinomas harboring micropapillary and/or solid components held higher rates of metastatic lymph node stations (25.2 % vs. 15.6 %, p = 0.002; and 24.0 % vs. 14.9 %, p < 0.001, respectively) and lymph nodes (17.3 % vs. 10.1 %, p = 0.004; and 15.5 % vs. 9.7 %, p = 0.001, respectively). Patients with micropapillary and solid components in their tumors showed a shorter median recurrence-free survival (15.8 vs. 62.8 months, p < 0.001; and 20.8 months vs. not reached, p < 0.001) and overall survival (47.0 months vs. not reached, p < 0.001; and 69.0 months vs. not reached, p < 0.001). Conclusions Minor components of micropapillary and/or solid subtypes of lung adenocarcinoma are correlated with lymph node metastasis and poor prognosis. Thus, it is beneficial to focus not only on predominant subtypes but also minor components to predict prognoses and make therapeutic strategies more comprehensively.
    No preview · Article · Feb 2016 · Annals of Surgical Oncology
  • Yang Zhang · Haiquan Chen · Yihua Sun

    No preview · Article · Feb 2016 · OncoTargets and Therapy
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    ABSTRACT: Introduction: Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increase risk of micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. Methods: Using a prospective database of patients with ESCC, 666 cases were retrospectively analysed to identify the relationship between LVI and survival, and to evaluate prognosis predictive accuracy after combining LVI and TNM system. Pathological slides were re-assessed by gastrointestinal pathologists according to the strict criteria. 1000-bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database for external validation. Results: LVI was present in 33.8%, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease-specific survival (DSS; HR=1.59; 95% CI, 1.30-1.94) and disease-free survival (DFS; HR=1.62; 95% CI, 1.32-1.98) after T classification. Among node-negative patients, LVI and T classification were two independent predictors of DSS and DFS (p<0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8% (p<0.001), respectively. The external validation showed congruent results. The DSS of TxN0MO with LVI was similar to the corresponding TxN1M0 (all p>0.05). In contrast, LVI was not associated with DSS or DFS among node-positive patients. Conclusions: The independent prognostic significance of LVI only existed in node-negative patients with ESCC, and the combination of LVI and TNM system enhanced the prognosis predictive accuracy. After confirmation, node-negative patients with LVI might be considered to be upstaged in pathological staging.
    Preview · Article · Jan 2016 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
  • Bin Li · Jiaqing Xiang · Yawei Zhang · Hong Hu · Yihua Sun · Haiquan Chen
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    ABSTRACT: Objective We aimed to clarify the association between anastomotic leak and leak-associated mortality to assist decision-making and reduce hospital mortality. Background Anastomotic leak is a common complication after esophagectomy, but the nature of its relationship to leak-associated mortality has not been established. Methods A retrospective review of all esophagogastric anastomotic leaks that had occurred between 2008 and 2012 at our institution (n = 246) was performed. Risk factors for leak-associated mortality were determined using a multivariate logistic regression analysis. Results Of the 246 patients with anastomotic leaks, 14 (5.7 %) died. Leak-associated mortality rates were similar regardless of anastomosis location (cervical vs. thoracic anastomosis), surgical approaches (retrosternal vs. prevertebral reconstruction route) and anastomotic techniques (hand-sewn vs. mechanical anastomosis). When a leak occurred, risk factors for leak-associated mortality as determined by multivariate logistic analysis included patient age >60 years (P = 0.029) and the occurrence of the leak within 1 week of surgery (P = 0.039). When disease worsened after treatment, leak-associated mortality was more frequent in patients requiring reintubation (25.6 vs. 1.4 %, P < 0.001). Fatal bleeding and sepsis were the most common causes of leak-associated mortality. Conclusion In patients with anastomotic leaks, patient age >60 years and the occurrence of the leak within 1 week of surgery were risk factors for leak-associated mortality. Increased efforts to reduce the incidence of early anastomotic leaks within 1 week after surgery and prevent the need for reintubation are important for improving patient prognosis.
    No preview · Article · Dec 2015 · World Journal of Surgery
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    ABSTRACT: Purpose: We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. Methods: We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Results: Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. Conclusions: ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.
    No preview · Article · Dec 2015 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: The aim of this retrospective study was to investigate the risk factors for bone metastases (BM) in clinical T1N0 non-small cell lung cancer (NSCLC) patients. From January 2010 to June 2012, 739 patients with primary diagnosed cT1N0 NSCLC were eligible for this study. Clinical variables, including sex, smoking history, age at diagnosis, tumor size, pathologic subtype, preoperative serum Carcino embryonie antigen (CEA) level, lesion imaging performance, and skeletal system symptom, were collected. BM were found in 7 patients (0.95%), in whom 6 patients had skeletal system symptom and 1 had silent metastasis. The frequency of BM was significantly high in younger patients (P = 0.007) and in patients with higher preoperative serum CEA level (P = 0.05). In multivariate analysis, age less than 50 years old (OR = 2.23, 95% CI: 1.56–4.21, P = 0.02), presence of clinical symptom (OR = 3.15, 95% CI: 1.98–6.42, P = 0.008), and CEA level over 5 μg/mL (OR = 2.14, 95% CI: 1.37–3.53, P = 0.03) were independently associated with BM in cT1N0 NSCLC patients. Presence of skeletal system symptom is not the unique criteria for performing BS. Younger age at diagnosis and higher preoperative serum CEA level are also risk factors for BM in cT1N0 NSCLC patients. Therefore, the selection of early-stage NSCLC patients being performed BS should be more precise in the future.
    No preview · Article · Dec 2015 · Medicine
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    ABSTRACT: Background: The role of EGFR tyrosine kinase inhibitors (TKIs) in the adjuvant treatment of non-small-cell lung cancer (NSCLC) has not been well established. Our meta-analysis aimed to determine whether the administration of EGFR-TKIs could improve the outcomes of patients with NSCLC undergoing complete resection. Methods: We comprehensively searched databases and extracted data from eligible studies. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) as well as disease relapse with Odds ratios (OR) were calculated using random and/or fixed-effects models. Meta-regression analysis and test for interaction between subgroups were also carried out. Results: A total of 1,960 patients in five studies were included. Adjuvant EGFR-TKIs treatment was associated with a significant benefit on DFS (HR 0.86, 95%CI 0.74-1.00), corresponding to an absolute benefit of 3.1% at 3 years, yet with significant heterogeneity (I(2)=83.4%, P<0.001). The survival benefit was superior (Pinteraction=0.03) in studies with over-18-month median treatment duration. EGFR mutation rate was also identified as a source of heterogeneity (P=0.017). In the EGFR-mutant population, HR for DFS was 0.48, (95%CI 0.36-0.65), corresponding to an absolute benefit of 9.5% at 3 years, with a reduced risk of distant metastasis (OR 0.71, 95%CI 0.56-0.92). Adjuvant EGFR-TKIs treatment resulted in a marginally statistically significant benefit on OS (HR 0.72, 95%CI 0.49-1.06). The rate of overall grade 3 or greater adverse events was 42.3% (95%CI, 39.1-45.6%). Conclusions: Adjuvant EGFR-TKIs treatment may enhance disease-free survival and reduce the risk of distant metastasis in EGFR-mutant NSCLC undergoing complete resection.
    Full-text · Article · Dec 2015 · Chest
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    ABSTRACT: Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09-0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC.
    Preview · Article · Dec 2015 · OncoTargets and Therapy
  • Xufeng Pan · Yong Chen · Jianxin Shi · Heng Zhao · Haiquan Chen
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    ABSTRACT: A 61-year-old man had experienced an irritating cough for 1 month. He received a diagnosis of lung adenocarcinoma by bronchoscopy. Computed tomography showed a mass in the left hilum and mediastinal lymph node enlargement. After two cycles of neoadjuvant chemotherapy, the patient underwent a robotic assisted atypical sleeve lobectomy (left lower lobe + S4+5). The patient's postoperative course was uneventful, and he was discharged on the tenth postoperative day. This is the first description of the feasibility of robotic extended sleeve lobectomy for a lung cancer patient receiving neoadjuvant chemotherapy.
    No preview · Article · Dec 2015 · The Annals of thoracic surgery
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    ABSTRACT: Background: Esophageal squamous cell carcinoma (ESCC) is the major histologic subtype of esophageal cancer, characterized by a high mortality rate and geographic differences in incidences. It is unknown whether there is difference between "eastern" ESCC and "western" ESCC. This study is attempted to demonstrate the hypothesis by comparing ESCC between Chinese residents and Caucasians living in the US. Methods: The data sources of this study are from United States SEER limited-use database and Shanghai Cancer Registries by Shanghai Municipal Center for Disease Control (SMCDC). Consecutive, non-selected patients with pathologically diagnosed ESCC, between January 1, 2002 and December 31, 2006, were included in this analysis. 1-year, 3-year and 5-year survival estimates were computed and compared between two populations. A Cox proportional hazards model was used to determine factors affecting survival differences. Results: A total of 1,718 Chinese, 1,624 Caucasians ESCC patients with individual American Joint Commission on Cancer (AJCC) staging information were included in this study. The Caucasian group had a significantly higher proportion of female patients than Chinese (38.24% vs. 18.68% P<0.01). ESCC was diagnosed in Chinese patients at an earlier age and stage than Caucasians. Generally, Chinese patients had similar overall survival rate with Caucasian by both univariate and multivariate analysis. Overall survival was significantly worse only in male Caucasians compared to Chinese patients (median survival time, 12.4 vs. 14.5 months, P<0.01, respectively). Conclusions: ESCC from eastern and western countries might have some different features. These differences need to be taken into account for the management of ESCC patients in different ethnic groups.
    No preview · Article · Dec 2015 · Journal of Thoracic Disease
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    ABSTRACT: Purpose: This study investigated the accuracy of intraoperative frozen section (FS) diagnosis for predicting the final pathology (FP) of peripheral small-sized lung adenocarcinoma and evaluated its usefulness in sublobar resection. Patients and methods: The records of 803 patients with clinical stage I peripheral lung adenocarcinoma who underwent sublobar resection for FS diagnosis to guide surgical strategy were reviewed. The surgical extension was mainly based on FS. The FS were stratified into atypical adenomatous hyperplasia, adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma. The diagnostic accuracy of FS, the reasons for the discrepancy between FS and FP, and the clinical influence of the FS errors were evaluated. To assess the survival of patients with different subtypes after surgery, 301 patients were identified for prognosis evaluation. Results: The total concordance rate between FS and FP was 84.4%. When atypical adenomatous hyperplasia, AIS, and MIA were classified together as a low-risk group, the concordance rate was 95.9%. Most discrepant cases were the underestimation of AIS and MIA. The diagnostic accuracy of FS for tumors ≤ 1 cm and larger than 1 cm in diameter was 79.6% and 90.8%, respectively (P < .01). The FS errors had significant clinical impact on 0.9% of the 803 patients due to insufficient resection. The 5-year recurrence-free survival rate (100%) was significantly better for the patients with AIS/MIA than for patients with invasive adenocarcinoma (74.1%, P < .01). Conclusion: Frozen pathology has a high concordance rate with FP. Precise diagnosis by intraoperative FS is an effective method to guide resection strategy for peripheral small-sized lung adenocarcinoma.
    Full-text · Article · Nov 2015 · Journal of Clinical Oncology
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    ABSTRACT: Objectives: SOX2 is a gene that encodes for a transcription factor, which functions as an activator or suppressor of gene transcription. SOX2 amplification and overexpression have been found in various types of tumors and play important roles in cancer cells. The aim of the study was to evaluate SOX2 expression and amplification in lung squamous cell carcinomas (SCCs) and to determine the relationship with main clinicopathologic features, patient prognosis, and common driver mutations. Materials and methods: SOX2 protein levels were measured by immunohistochemistry, while SOX2 copy numbers were measured by fluorescence in situ hybridization in resected samples from 162 Chinese lung SCC patients. All patients were also analyzed for mutations in EGFR, HER2, BRAF, PIK3CA, NFE2L2, and FGFR fusion genes. Clinical characteristics, including age, sex, smoking status, stage, relapse-free survival (RFS), and overall survival (OS), were collected. Results: SOX2 overexpression and amplification were observed in 58.6% and 45.9% of lung SCCs. Lung SCC patients with SOX2 overexpression were significantly associated with absence of malignant tumor family history (P=0.021), FGFR fusion gene (P=0.046), longer RFS (P=0.041), and OS (P=0.025). No correlation was found between SOX2 gene amplification and main clinicopathologic features, patient prognosis, or common driver mutations. Conclusion: SOX2 overexpression and amplification are common in lung SCCs. SOX2 over-expression was associated with FGFR fusion genes and predicted favorable outcome in lung SCCs. The underlying relationship of SOX2 and FGFR still needs further investigation.
    Full-text · Article · Nov 2015 · OncoTargets and Therapy
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    ABSTRACT: Objective: B-cell-lymphoma-2 (Bcl-2) is a proto-oncogene that plays an important role in the regulation of apoptosis and cell survival. However, there are much conflicting data in the literature concerning the association between Bcl-2 and prognosis in non-small-cell lung cancer (NSCLC). There is little in the way of meta-analysis focused on Bcl-2 and its effect on NSCLC prognosis. This study was performed to provide an assessment of whether expression levels of Bcl-2 are associated with prognosis in patients with NSCLC. Materials and methods: We searched PubMed, the Cochrane Library, and China National Knowledge Infrastructure for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival were evaluated. Results: Fifty published studies including 6,863 patients with lung cancer were included in this meta-analysis. Overall, Bcl-2 was expressed in 33% of the NSCLC tumors studied. Our analysis indicates that NSCLC patients with Bcl-2-positive expression have a better prognosis than those with Bcl-2-negative expression in both Asian and non-Asian study populations (HR 0.79, 95% CI 0.72-0.87, P<0.00001). However, Bcl-2-positive expression seems to have no significant impact on survival of stage I NSCLC patients. Conclusion: Our results indicated that Bcl-2 might be a useful prognostic marker for NSCLC generally. Larger clinical trials are needed to confirm the prognostic value of Bcl-2 in stage I NSCLC.
    Preview · Article · Nov 2015 · OncoTargets and Therapy
  • Jian Xiong · Rui Wang · Yihua Sun · Haiquan Chen
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    ABSTRACT: Background The aim of this study was to evaluate the clinical features of T1aN2M0 stage non-small cell lung cancer (NSCLC).Method From November 2008 to May 2013, 498 patients with T1a-stage NSCLC who visited the Shanghai Cancer Center were included in the study. All patients underwent a lobectomy or segmentectomy with systematic nodal resection for primary lung cancer. Analyses of gender, smoking history, primary tumor site, tumor location, tumor size, pathological classification, cancer gene, pleural invasion, number of positive lymph nodes, skip N2, single or multiple station N2, progression-free survival (PFS), and overall survival (OS) were performed.ResultThere were significant differences in tumor size, tumor size distribution, adenocarcinoma subgroup, and number of positive lymph nodes between patients at T1aN2M0 and T1aN0M0 stages. The most common histology of the T1aN2M0 subgroup was adenocarcinoma. Epidermal growth factor receptor mutations were the most common gene mutation in T1aN2M0 stage NSCLC. There were significant differences in five-year OS and PFS rates between patients with T1aN2M0, T1aN0M0, and T1aN1M0 stages. Multivariate analyses of mediastinal lymph node metastasis showed that gender, tumor size distribution, and histology type were significant predictive factors. Multivariate analyses of OS and PFS rates in the T1aN2M0 subgroup showed that the number of positive lymph nodes was a significant predictive factor.Conclusion Gender, tumor size distribution, and histology type were independent predictors of mediastinal lymph node metastasis in patients with T1a stage. The number of positive lymph nodes was significantly associated with OS and PFS rates in patients with T1aN2M0 stage NSCLC.
    No preview · Article · Nov 2015 · Thoracic Cancer
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    ABSTRACT: Purpose: To determine the frequency of driver mutations in Chinese non-small cell lung cancer (NSCLC) patients. Methods: Comprehensive mutational analysis was performed in 1356 lung adenocarcinoma, 503 squamous cell carcinoma, 57 adenosquamous lung carcinoma, 19 large cell carcinoma and 8 sarcomatoid carcinoma. The effect of EGFR tyrosine kinase inhibitors (TKIs) on EGFR-mutated lung adenocarcinoma patients after disease recurrence was investigated. Results: Mutations in EGFR kinase domain, HER2 kinase domain, KRAS, BRAF, ALK, ROS1 and RET were mutually exclusive. In lung adenocarcinoma cases "pan-negative" for the seven above-mentioned driver mutations, we also detected two oncogenic EGFR extracellular domain mutations (A289D and R324L), two HER2 extracellular and transmembrane domain mutations (S310Y and V659E), one ARAF S214C mutation and two CD74-NRG1 fusions. Six (1.2%) FGFR3 activating mutations were identified in lung squamous cell carcinoma (five S249C and one R248C). There were three (15.8%) EGFR mutations and four (21.1%) KRAS mutations in large cell carcinoma. Three (37.5%) KRAS mutations were detected in sarcomatoid carcinoma. In EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence, treatment with EGFR TKIs was an independent predictor of better overall survival (HR = 0.299, 95% CI: 0.172-0.519, P < 0.001). Conclusion: We determined the frequency of driver mutations in a large series of Chinese NSCLC patients. EGFR TKIs might improve the survival outcomes of EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence.
    Preview · Article · Oct 2015 · Oncotarget
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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.
    Preview · Article · Sep 2015 · Scientific Reports
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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.
    Preview · Article · Sep 2015 · Journal of Experimental & Clinical Cancer Research
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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.
    Full-text · Article · Aug 2015 · Scientific Reports
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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.
    Preview · Article · Jul 2015 · Annals of Surgical Oncology
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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.
    No preview · Article · Jul 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

Publication Stats

2k Citations
700.03 Total Impact Points

Institutions

  • 2015
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2010-2015
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
  • 2007-2015
    • Fudan University
      • Department of Oncology
      Shanghai, Shanghai Shi, China
  • 2012
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, Massachusetts, United States