Chao-Nan Qian

Sun Yat-Sen University Cancer Center, Shengcheng, Guangdong, China

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Publications (99)489.77 Total impact

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    ABSTRACT: We previously reported the five-year results of a randomised trial that compared induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) with induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was to report the ten-year results and to explore potential prognostic factors. From August 2002 to April 2005, 408 patients with locoregionally advanced NPC were randomly assigned to receive either IC (carboplatin and floxuridine)+CCRT (carboplatin) or IC+RT. The survival rates were analysed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. The ten-year overall survival, failure-free survival, locoregional failure-free survival and distant failure-free survival rates for the entire patient cohort were 49.5%, 48.0%, 80.8% and 66.9%, respectively. No significant survival differences were found between the IC+CCRT and IC+RT arms. By 3years from the date of randomisation, 62.5% of the relapses had been detected; no recurrence occurred after 8years. Within 3years after randomisation, 77.0% of the metastases were detected; 0.8% was identified after 8years. Age, Union for International Cancer Control (UICC) N-stage, serum lactate dehydrogenase (LDH) and body mass index (BMI) were independent prognostic factors that predicted death. Smoking status and total radiotherapy dose were independent prognostic factors that predicted locoregional recurrence. UICC N-stage, LDH and BMI were independent prognostic factors that predicted distant metastasis. Concurrent carboplatin chemotherapy did not significantly improve the long-term survival after inductive carboplatin and floxuridine chemotherapy in locoregionally advanced nasopharyngeal carcinoma. In addition to patient and tumour characteristics, LDH, BMI and smoking status were important baseline prognostic factors for tumour recurrence or distant metastasis; these are worthy of further prognostic investigation in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 06/2015; DOI:10.1016/j.ejca.2015.05.025 · 4.82 Impact Factor
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    ABSTRACT: Recurrent tumour, node and metastasis (rTNM) stage system does not have an outstanding prognostic value for survival outcome of patients with recurrent nasopharyngeal carcinoma (rNPC) and it cannot aid the clinicians to choose the most suitable treatment for these patients. In total, 894 rNPC patients were consecutively enroled. All recurrent (r) tumour (T) stages (rT) and node (N) stages (rN) were stratified as resectable and unresectable based on the imaging data of the head and neck. These stages were re-subdivided into surgical T stages (sT) and surgical N stages (sN) with similar clinical characteristics and death risks and were re-integrated into a new 'surgical' stage using a Cox proportional hazards model. The 5-year overall survival (OS) was 72.0%, 55.1%, 21.1% and 10.1% in 'surgical' stages I, II, III and IV, respectively (P<0.001). The 'surgical' stage was a significant independent prognostic factor for OS (hazard ratio [HR] 1.78, P<0.001) and exhibited enhanced prognostic value compared with the rTNM staging system (area under receiver operating characteristics 0.68 versus 0.63, P<0.001). Endoscopic nasopharyngectomy and intensity-modulated radiation therapy were significant independent positive prognostic factors for the OS of patients with primary lesions in 'surgical' stage I/II and 'surgical' stage III, respectively (P<0.05). A combination of aggressive treatments for loco-regional lesions exhibited a beneficial trend for OS of patients with 'surgical' stage IV (P>0.05). Compared with the rTNM stage system, the 'surgical' staging system exhibited enhanced prognostic value for rNPC patient survival and could aid clinicians in choosing the most suitable treatment for rNPC patients. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 06/2015; 110. DOI:10.1016/j.ejca.2015.05.014 · 4.82 Impact Factor
  • PLoS ONE 04/2015; 10(4):e0122965. DOI:10.1371/journal.pone.0122965 · 3.53 Impact Factor
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    ABSTRACT: To evaluate and compare the prognostic value of Epstein-Barr virus (EBV) DNA and maximal standard uptake values (SUVmax ) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) in subgroups of nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence. A total of 194 patients with recurrent NPC (locoregional recurrence: 107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence performed with 18F-FDG-PET and an EBV DNA test before salvage treatment. Clinical parameters, the status of EBV DNA and the value of SUVmax were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards regression model. In the subgroup of patients with locoregional recurrence, patients with SUVmax<8.65 had significantly better overall survival (OS) (P=0.005) compared with the patients with SUVmax ≥8.65. However, both elevated EBV DNA load (≥21,100 copies/ml) and distant SUVmax (≥13.55) were significantly associated with worse OS compared with the patients with EBV DNA <21,100 copies/ml or distant SUVmax <13.55 for the subgroup with distant recurrence (P=0.015 and P=0.006, respectively). The predictive ability of EBV DNA was superior to that of SUVmax (P=0.062). Multivariate analysis showed that SUVmax was only an independent prognostic factor for OS in patients with locoregional recurrence (P=0.042), whereas EBV DNA independently predicted OS for the patients with distant recurrence (P=0.007). For those patients with undetectable EBV DNA, SUVmax<8.65 was still an independent favorable prognostic factor (P=0.038). SUVmax is a useful biomarker for predicting OS in nasopharyngeal carcinoma patients with locoregional recurrence or with undetectable EBV DNA. Both distant SUVmax and EBV DNA appear to be independent predictors of OS in patients with distant recurrence; however, the predictive ability of EBV DNA was superior to that of SUVmax.
    PLoS ONE 04/2015; 10(4):e0122756. DOI:10.1371/journal.pone.0122756 · 3.53 Impact Factor
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    ABSTRACT: The impact of standard chemo-radiotherapy (CRT) as preferred therapy for elderly patients (age≥60 years) with nasopharyngeal carcinoma (NPC) remains unclear. Therefore, a strict matched cohort study was conducted to compare the survival and treatment toxicity of standard chemo-radiotherapy in the elderly NPC patients with those of radiotherapy (RT) alone. From 1998 to 2003, total 498 newly diagnosed elderly non-metastatic NPC patients were abstracted and classified into two groups by the treatments they received. For each patient in the CRT group, a matched pair in RT group was identified by matching for gender, age, histological type, T and N classifications, RT dose to primary tumor and neck nodes, and days of radiotherapy. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared between the two groups. Two groups were well balanced in clinical characteristics because of the strict matching conditions. Totally 87 pairs can be assessed according to the criteria. The 5-year OS, CSS, FFS, and LR-FFS for CRT and RT groups were 62% versus 40% (P=0.013), 67% versus 47% (P=0.018), 65% versus 53% (log-rank: P=0.064, Breslow: P=0.048), and 88% versus 72%, (P=0.019), respectively. There was no significant difference in 5-year D-FFS between the two groups (75% vs. 73%, P=0.456). The CRT group experienced significantly more Grade ≥3 acute mucositis (46.0% vs. 28.7%, P= 0.019). We concluded that standard chemo-radiotherapy can achieve a reasonable local and regional control in elderly NPC patients with acceptable and reversible acute toxicity. However, distant metastasis remains the dominant failure pattern. When the elderly NPC patients are in good performance status following a complete evaluation of overall functional status and comorbidity conditions, standard chemo-radiotherapy is worthy of recommendation.
    PLoS ONE 03/2015; 10(3):e0119593. DOI:10.1371/journal.pone.0119593 · 3.53 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) has the highest metastasis rate among head and neck cancers with unclear mechanism. WNT5A belongs to the WNT family of cysteine-rich secreted glycoproteins. Our previous high-throughput gene expression profiling revealed that WNT5A was up-regulated in highly metastatic cells. In the present study, we first confirmed the elevated expression of WNT5A in metastatic NPC tissues at both the mRNA and protein levels. We then found that WNT5A promoted epithelial-mesenchymal transition (EMT) in NPC cells, induced the accumulation of CD24-CD44+ cells and side population, which are believed to be cancer stem cell characteristics. Moreover, WNT5A promoted the migration and invasion of NPC cells in vitro, while in vivo treatment with recombinant WNT5A promoted lung metastasis. Knocking down WNT5A diminished NPC tumorigenesis in vivo. When elevated expression of WNT5A coincided with the elevated expression of vimentin in the primary NPC, the patients had a poorer prognosis. Among major signaling pathways, protein kinase C (PKC) signaling was activated by WNT5A in NPC cells. A positive feedback loop between WNT5A and phospho-PKC to promote EMT was also revealed. Taken together, these data suggest that WNT5A is an important molecule in promoting stem cell characteristics in NPC, leading to tumorigenesis and metastasis.
    Oncotarget 03/2015; · 6.63 Impact Factor
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    ABSTRACT: Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating lymphocytes (TILs) can induce immune responses and antitumor activity in metastatic melanoma patients. Here, we aimed to assess the safety and antitumor activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty-three newly diagnosed, locoregionally advanced NPC patients were enrolled, of whom 20 received a single-dose of TIL infusion following CCRT. All treated patients were assessed for toxicity, survival and clinical and immunologic responses. Correlations between immunological responses and treatment effectiveness were further studied. Only mild adverse events (AEs), including Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were observed. Nineteen of 20 patients exhibited an objective antitumor response, and 18 patients displayed disease-free survival longer than 12 mo after ACT. A measurable plasma Epstein-Barr virus (EBV) load was detected in 14 patients at diagnosis, but a measurable EBV load was not found in patients after one week of ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral blood following TIL therapy were observed in 13 patients. The apparent positive correlation between tumor regression and the expansion of T cells specific for EBV was further investigated in four patients. This study shows that NPC patients can tolerate ACT with TILs following CCRT and that this treatment results in sustained antitumor activity and anti-EBV immune responses. A larger phase II trial is in progress.
    OncoImmunology 02/2015; 4(2):e976507. DOI:10.4161/23723556.2014.976507 · 6.28 Impact Factor
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    ABSTRACT: To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of nasopharyngeal carcinoma (NPC). Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared. Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging. Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease. Copyright © 2014 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 12/2014; 91(2). DOI:10.1016/j.ijrobp.2014.10.005 · 4.18 Impact Factor
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    ABSTRACT: Background The aim of this study was to investigate the prognostic significance and various classifications for anatomic masticator space involvement (MSI) in patients with nasopharyngeal carcinoma (NPC). Methods This study retrospectively analyzed 742 patients with untreated nondisseminated NPC who underwent magnetic resonance imaging (MRI) scan of the nasopharynx and neck. The MSI was graded according to different anatomic features. The overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) of the patients with different MSI grades were analyzed using the Kaplan-Meier method and log-rank tests. Results The frequency of MSI was 24.1% (179/742). The 5-year OS, LRFS, DMFS, DFS for NPC patients with versus without MSI were 70.9% versus 82.5% (P = 0.001), 94.1% versus 91.4% (P = 0.511), 81.4% versus 88.7% (P = 0.021), and 78.0% versus 83.5% (P = 0.215), respectively. Significant differences in OS were also found among different MSI groups. In the patients with MSI, the OS of the group with medial and/or lateral pterygoid involvement (MLPI) NPC was 73.9% compared to 51.3% (P < 0.0001) in the patients with infratemporal fossa involvement (IFI). Conclusions MSI was an independent prognostic factor for OS and DMFS. NPCs invading the masticator space should be separately categorized into MLPI and IFI prognostic groups. We suggest that MLPI should be staged as T3 while IFI is staged as T4 disease in future TNM staging revision.
    BMC Cancer 09/2014; 14(1):653. DOI:10.1186/1471-2407-14-653 · 3.32 Impact Factor
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    Ai zheng = Aizheng = Chinese journal of cancer 08/2014; 33(8):367-8. DOI:10.5732/cjc.014.10115
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    ABSTRACT: The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. Serum lipids and lipoproteins have been reported to be associated with prognosis in some cancers, but it has not been studied in metastatic NPC. The aim of this study was to evaluate whether serum lipid and lipoproteins could predict the prognosis of metastatic NPC patients. Eight hundred and seven patients with metastatic NPC were analyzed retrospectively, and the values of serum lipids and lipoproteins at baseline were retrieved. Receiver operating characteristic curve analysis and univariate and multivariate Cox proportional hazards analyses were used to evaluate the associations of serum lipids and lipoproteins with overall survival (OS). Univariate analysis revealed that higher values of baseline cholesterol (≥4.655 mmol/L), baseline high-density lipoprotein cholesterol (≥0.965 mmol/L), and baseline apolipoprotein A-I (ApoA-I) (≥1.065 g/L) were significantly associated with superior OS (p < 0.001), respectively. Multivariate Cox proportional hazard analysis showed that higher ApoA-I level (vs. lower ApoA-I level, HR 0.64, 95 % CI 0.52-0.80, p < 0.001) was an independent protective factor against progression. In addition, higher body mass index, earlier N stages, single lesion, and absence of liver metastasis were also revealed to be independent protective factors. In conclusion, the elevated baseline ApoA-I level may predict those patients likely to have a favorable OS.
    Medical Oncology 08/2014; 31(8):80. DOI:10.1007/s12032-014-0080-y · 2.06 Impact Factor
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    ABSTRACT: Radiation and cisplatin-based chemotherapy are major treatments for nasopharyngeal carcinoma (NPC). However, a major impediment for further improving the cure rate is the development of treatment resistance with an undetermined molecular mechanism in metastatic NPC cells. Our established, highly metastatic NPC cells have been reported to be more resistant to cisplatin chemotherapy. In the present study, we found that Ras association domain family member 6 (RASSF6) was downregulated in highly metastatic cells but upregulated in low metastatic cells in comparison to their parental cell line. Ectopic-expression of RASSF6 enhanced the sensitivity of highly metastatic NPC cells to cisplatin or radiation by enhancing apoptosis. RASSF6 depletion conversely reduced treatment sensitivity by decreasing the apoptosis rate. Over-expression of RASSF6 in highly metastatic NPC cells could enhance the phosphorylation of JNK when exposed to cisplatin or radiation treatment, while knocking down RASSF6 in low metastatic NPC cells could reduce the level of phospho-JNK when exposed to the same treatments. The activation of JNK signaling by RASSF6 and its subsequent sensitivity to apoptosis in NPC cells could be inhibited by applying the JNK inhibitor SP600125. In conclusion, the downregulation of RASSF6 in highly metastatic NPC cells contributed to their treatment resistance, and over-expression of RASSF6 conferred treatment sensitivity to highly metastatic NPC cells by activating JNK signaling. RASSF6 could be a valuable molecular marker for identifying sensitive metastatic NPC tumors during cisplatin treatment or radiotherapy.
    PLoS ONE 07/2014; 9(7):e100843. DOI:10.1371/journal.pone.0100843 · 3.53 Impact Factor
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    ABSTRACT: We aimed to determine the prognostic values of 39 circulating cytokines in Chinese patients with metastatic colorectal cancer (CRC) and to develop a novel cytokine-based prognostic classifier (CBPC) for prognostic prediction. A total of 176 patients were divided into two cohorts based on the date of first-line chemotherapy. The first 99 cases were assigned to the training cohort, and the remaining 77 cases were assigned to the validation cohort. Thirty-nine cytokines were simultaneously analyzed in the patient serum samples using multiplex bead-based Luminex technology. We used support vector machine (SVM)-based methods and Cox proportional hazards models to develop a CBPC from the training cohort, which we then validated using the second patient cohort. Univariate analysis showed that FGF-2, TGFα, Flt-3L, GM-CSF, INFα2, GRO, IL-10, MCP-3, MDC, sIL-2Rα, IL-2, IL-7, IL-8, MCP-1, MIP-1β, TNFα, and VEGF were significant risk factors affecting the overall survival (OS) of both the training cohort and the validation cohort. We developed a CBPC to predict the OS of metastatic CRC patients using these 17 cytokines (sensitivity, 0.835; specificity, 0.800). In the validation cohort, the CBPC was found to have significant power in predicting the OS of metastatic CRC patients. Our study showed that there were significant associations between cytokine expression and prognosis of the patients with metastatic CRC. The CBPC that we developed includes multiple circulating cytokines and may serve as a novel screening tool for identifying metastatic CRC patients with a high risk of short OS. These high-risk individuals may also be suitable for cytokine-targeted therapies. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2014; DOI:10.1002/ijc.29017 · 5.01 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.
    Cell cycle (Georgetown, Tex.) 04/2014; 13(12). DOI:10.4161/cc.28921 · 5.01 Impact Factor
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    Wei Zhang, Chao-Nan Qian, Yi-Xin Zeng
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    ABSTRACT: Once considered a taboo topic or stigma, cancer is the number one public health enemy in the world. Once a product of an almost untouchable industry, tobacco is indisputably recognized as a major cause of cancer and a target for anti-cancer efforts. With the emergence of new economic powers in the world, especially in highly populated countries such as China, air pollution has rapidly emerged as a smoking gun for cancer and has become a hot topic for public health debate because of the complex political, economic, scientific, and technological issues surrounding the air pollution problem. Does air pollution cause a wide spectrum of cancers? Should air pollution be considered a necessary evil accompanying economic transformation in developing countries? Is an explosion of cancer incidence coming to China and how soon will it arrive? What must be done to prevent this possible human catastrophe?
    Ai zheng = Aizheng = Chinese journal of cancer 03/2014; 33(4). DOI:10.5732/cjc.014.10034
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    ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is a highly aggressive and common pathological subtype of renal cancer. This cancer is characterized by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene, which leads to the accumulation of hypoxia-inducible factors (HIFs). Although therapies targeted at HIFs can significantly improve survival, nearly all patients with advanced ccRCC eventually succumb to the disease. Thus, additional oncogenic events are thought to be involved in the development of ccRCC tumors. In this study, we investigated the role of RASSF6 in ccRCC. Downregulation of RASSF6 was commonly observed in primary tumors relative to matched adjacent normal tissues. Moreover, functional studies established that ectopic re-expression of RASSF6 in ccRCC cells inhibited cell proliferation, clonogenicity, and tumor growth in mice, whereas silencing of RASSF6 dramatically enhanced cell proliferation in vitro and in vivo. Mechanistic investigation suggested that RASSF6 triggers p21(Cip1/Waf1) accumulation to induce G 1 cell cycle arrest and promote apoptosis upon exposure to pro-apoptotic agents, and both of these mechanisms appear to be mediated by activated JNK signaling. Together, these findings suggest that RASSF6 may play a tumor suppressor role in the progression of ccRCC.
    Cell cycle (Georgetown, Tex.) 03/2014; 13(9). DOI:10.4161/cc.28416 · 5.01 Impact Factor
  • Wei-Wei Xiao, Chao-Nan Qian
    Ai zheng = Aizheng = Chinese journal of cancer 03/2014; 33(3):125-132. DOI:10.5732/cjc.014.10021
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    ABSTRACT: Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction. After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms. Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.
    PLoS ONE 12/2013; 8(12):e82750. DOI:10.1371/journal.pone.0082750 · 3.53 Impact Factor
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    ABSTRACT: Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray. In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) (p=0.02), Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2 (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03) and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased. All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.
    European journal of cancer (Oxford, England: 1990) 12/2013; 50(3). DOI:10.1016/j.ejca.2013.11.007 · 4.82 Impact Factor

Publication Stats

2k Citations
489.77 Total Impact Points

Institutions

  • 2008–2015
    • Sun Yat-Sen University Cancer Center
      • Department of Radiation Oncology
      Shengcheng, Guangdong, China
  • 2003–2014
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Shengcheng, Guangdong, China
  • 2002–2013
    • Van Andel Research Institute
      Grand Rapids, Michigan, United States
  • 2010
    • National Cancer Centre Singapore
      • Division of Clinical Trials and Epidemiological Sciences
      Singapore
  • 2005
    • Calvin College
      • Department of Biology
      Grand Rapids, Michigan, United States