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Hao L.,Tianjin Medical University | Hao L.,Key Laboratory of Cancer Prevention and Therapy | Hao L.,Tianjin Lung Cancer Center | Zhao X.,Tianjin Medical University | And 11 more authors.
Tumor Biology | Year: 2015

This study aims to investigate the expression level of pro-opiomelanocortin (POMC) and its prognostic value in non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression level of POMC. Correlations between POMC expression and clinical and pathological characteristics were evaluated with the chi-square test, and the prognostic value was determined with the Kaplan–Meier method and COX proportional hazards model, α < 0.05. Of the samples, 48.0 % had positive POMC expression. POMC expression was significantly related to poorly differentiated tumors, N-stage, p-stage, postoperative failure pattern, expression of vimentin, and expression of E-cadherin (P < 0.05). Multivariate analysis revealed that POMC-positive expression was an independent risk factor for disease-free survival (hazard ratio (HR) 1.988, 95 % confidence interval (CI) 1.094–3.910, P = 0.024) and overall survival (HR 1.892, 95 % CI 1.726–3.709, P = 0.036). The addition of POMC protein expression to the prognostic model using pathological stage markedly improved the prognostic potential, and the area under the ROC increased from 0.691 to 0.775. Further study revealed that patients with POMC-negative expression can benefit more from a regimen of paclitaxel and carboplatin chemotherapy than a regimen of vinorelbine and carboplatin compared to patients with POMC-positive expression. We found that POMC-positive expression is a novel, independent poor prognostic marker in patients with NSCLC. Prospective studies are needed to validate the potential prognostic value of POMC in combination with the current staging system and in consideration of adjuvant chemotherapy. © 2014, International Society of Oncology and BioMarkers (ISOBM). Source

Zhang H.,Tianjin Medical University | Zhang H.,Key Laboratory of Cancer Prevention and Therapy | Zhang H.,Tianjin Lung Cancer Center | Zhang L.,Tianjin Medical University | And 21 more authors.
PLoS ONE | Year: 2015

Introduction: The aim of this study was to investigate the prognostic significance of the combination of the preoperative platelet count and neutrophil-lymphocyte ratio (COP-NLR) for predicting postoperative survival of patients undergoing complete resection for non-small cell lung cancer (NSCLC). Methods: The preoperative COP-NLR was calculated on the basis of data obtained.Patients with both an increased platelet count (>30.0×104 mm-3) and an elevated NLR (>2.3) were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively. Results: A total of 1238 NSCLC patients were enrolled in this analysis. Multivariate analysis using the 15 clinicolaboratory variables selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for DFS (HR: 1.834, 95%CI: 1.536 to 2.200, P<0.001) and OS (HR: 1.810, 95%CI: 1.587 to 2.056, P<0.001). In subanalyses by tumor stage (I, II, IIIA), a significant association was found between DFS and OS and level of COP-NLR in each subgroup (P<0.001, P=0.002, P<0.001 for DFS, respectively; P<0.001, P=0.001, P<0.001 for OS). When the subgroup of patients with high-risk COP-NLR (score of 2) was analyzed, no benefit of adjuvant chemotherapy could be found (P=0.237 for DFS and P=0.165 for OS). Conclusions: The preoperative COP-NLR is able to predict the prognosis of patients with NSCLC and divide these patients into three independent groups before surgery. Our results also demonstrate that high-risk patients based on the COP-NLR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted. © 2015 Zhang et al. Source

Zhao H.,Tianjin Medical University | Zhao H.,Key Laboratory of Cancer Prevention and Therapy | Zhao H.,Tianjin Lung Cancer Center | Li H.,Tianjin Medical University | And 23 more authors.
Chinese Journal of Clinical Oncology | Year: 2010

Objective: To investigate the expression of TSLP in human lung cancer tissue and the correlation between TSLP expression and number of regulatory T cells (Tregs). Methods: The expression of TSLP mRNA and protein was detected in different pathological lesions of the lung by Q-RT-PCR and immunohistochemistry. Immunohistochemistry was used to detect Foxp3+ Tregs. The correlation of TSLP with the number of Tregs was analyzed. Results: TSLP gene was expressed in tumor tissues (n=37), latero-tumor tissues (n=29) and non-tumor lung tissues (n=24), without statistical difference (P=0.148). TSLP protein was expressed in the cytoplasm and was observeed in 69.57% of tumor tissues, 13.33% of benign lesions and 30.00% of non-tumor lung tissues, with a significant difference (P<0.05). The expression of TSLP protein was correlated with tumor size (P=0.000) and lymph node metastasis (P=0.018). The number of Tregs in TSLP positive group was more than that in TSLP negative group (P<0.05). Conclusion: The expression of TSLP in lung tumor tissues is increased and is correlated with the number of Tregs, indicating that TSLP could induce Treg to play an important role in tumor immunotolerance. Source

Li C.,Tianjin Medical University | Li C.,Key Laboratory of Cancer Prevention and Therapy | Li C.,Tianjin Lung Cancer Center | Hao L.,Tianjin Medical University | And 31 more authors.
PLoS ONE | Year: 2014

Introduction: Targeting activating oncogenic driver mutations in lung adenocarcinoma has led to prolonged survival in patients harboring these specific genetic alterations. The prognostic value of these mutations has not yet been elucidated. The prevalence of recently uncovered non-coding somatic mutation in promoter region of TERT gene is also to be validated in lung cancer. The purpose of this study is to show the prevalence, association with clinicalpathological features and prognostic value of these factors. Methods: In a cohort of patients with non-small cell lung cancer (NSCLC) (n = 174, including 107 lung adenocarcinoma and 67 lung squamous cell carcinoma), EGFR, KRAS, HER2 and BRAF were directly sequenced in lung adeoncarcinoma, ALK fusions were screened using FISH (Fluorescence in situ Hybridization).TERT promoter region was sequenced in all of the 174 NSCLC samples. Associations of these somatic mutations and clinicopathological features, as well as prognostic factors were evaluated. Results: EGFR, KRAS, HER2, BRAF mutation and ALK fusion were mutated in 25.2%, 6.5%, 1.9%, 0.9% and 3.7% of lung adenocarcinomas. No TERT promoter mutation was validated by reverse-sided sequencing. Lung adenocarcinoma with EGFR and KRAS mutations showed no significant difference in Disease-free Survival (DFS) and Overall Survival (OS). Cox Multi-variate analysis revealed that only N stage and HER2 mutation were independent predictors of worse overall survival (HR = 1.653, 95% CI 1.219-2.241, P = 0.001; HR = 12.344, 95% CI 2.615-58.275, P = 0.002). Conclusions: We have further confirmed that TERT promoter mutation may only exist in a very small fraction of NSCLCs. These results indicate that dividing lung adenocarcinoma into molecular subtypes according to oncogenic driver mutations doesn't predict survival difference of the disease. © 2014 Li et al. Source

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