| ObjectiveLung cancer has been the leading cause of cancer-related death all around the word. To investigate the marker of early diagnosis and prognosis of lung cancer, the expression level of POMC, correlation between POMC and markers of EMT and its prognostic value and the prognostic value of driver mutations in NSCLC were investigated.Method1. According to the exclusion and inclusion criterion, 5 pairs of new tissues of non-small cell lung cancer and 102 paraffin-embedded non-small cell lung cancer tissues from patients between January 2004 and January 2008 in Cancer Institute and Hospital of Tianjin Medical University were selected in the study of POMC and 174 tissues in the study of driver mutations. Records of all patients were reviewed in detail and analyzed.2. Expression of POMC in 5 pairs of new tissues were detected using western blot.Immunohistochemistory staining was used to detect the expression level of POMC,E-cadherin and Vimentin in 102 paraffin-embedded non-small cell lung cancer tissues.PCR and sequencing were used to analysis of the prognostic value of driver mutations.3. Correlations between the expression of POMC and clinicopathological parameters and correlations between the expression of POMC and markers of EMT,including E-cadherin and Vimentin, were analysed using the χ2 test. The Kaplan-Meier method and the Log-rank test were used to calculate Overall survival(OS) and Disease-free survival(DFS). A prognostic analysis was carried out using univariate and multivariate Cox regressions models. Receiver operator characteristic curve(ROC) was used to analyze the prognostic potential. The larger was the area under ROC, the more prognostic potential the factors had.4. A new predictive model was established with combination of POMC expression and TNM staging system Results1. Expression of POMC was detected in 2 pairs of new tissues, using western blot. 49(48.0%) samples were observed with positive expression of POMC, mainly observed in cytoplasm. Positive expression of E-cadherin was observed on membrane,with positive ratio 42.3%(43 patients). Vimentin was localised to the stromalstructures of normal or neoplastic tissues, as well as the cytoplasm of the neoplastic tissues, with positive ratio 47.1%(48 patients).2. POMC expression was significantly related to poorly differentiated tumors,female, advanced TNM stage, postoperative failure pattern, expression of Vimentin and expression of E-cadherin, P<0.05.3. Multivariate analysis revealed that POMC positive expression was independent risk factors for disease free survival(HR 1.988, 95%CI 1.094-3.910,P=0.024) and overall survival(HR 1.892, 95%CI 1.726-3.709, P=0.036). 5-year OS of patients with POMC positive expression and negative expression were 29.6% and65.5% respectively, and 5-year DFS were 24.1% and 65.6%. POMC was the most potential prognostic factor. But EGFR and KRAS showed no prognostic value.4. The addition of POMC protein expression to the prognostic model using pathologic stage markedly improved the prognostic potential, the area under ROC increased from 0.689 to 0.778.Conclusion1. POMC was related to much more advanced TNM stage, poorer differentiated tumors revealed tumor with POMC positive expression was much more malignant.2. Correlations between POMC and E-cadherin and Vimentin showed that POMC may influence the development of tumor by the process of EMT.3. POMC positive expression is a novel independent poor prognostic marker of patients with NSCLC. EGFR and KRAS showed no prognostic value,though they showed significant influence in patients with target-therapy.4. Much more accurate prognostic model need the combination of TNM staging system and prognostic molecular makers. |
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