Clinical Research Papers:
Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer
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Bangrong Cao1,2, Lin Feng1, Dan Lu1, Yan Liu1, Yu Liu1, Suping Guo1, Naijun Han1, Xiangyang Liu3, Yousheng Mao3, Jie He3, Shujun Cheng1, Yanning Gao1 and Kaitai Zhang1
1 State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
2 Department of Basic Research, Sichuan Cancer Hospital & Institute, Chengdu, Sichuan Province, China
3 Department of Thoracic Surgical Oncology, Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Kaitai Zhang, email:
Yanning Gao, email:
Shujun Cheng, email:
Keywords: negative surgical margin, epithelial-to-mesenchymal transition, prognosis, non-small-cell lung cancer, gene-expression signature
Received: June 13, 2016 Accepted: July 19, 2016 Published: July 29, 2016
It is hypothesized that the molecular status in negative surgical margin (NSM) is associated with prognosis of cancer patients. In this study, the prognostic relevance of Epithelial-to-Mesenchymal Transition (EMT) molecular events in NSMs in patients with NSCLC was investigated. EMT model was developed, in which the mesenchymal transition of human immortalized bronchial epithelial cell line was induced by TGF-beta1. Gene expression of EMT-induced cells and NSMs from 60 lung squamous cell carcinoma (SCC) patients was profiled by microarray and validated by quantitative RT-PCR. Two independent cohorts (lung SCC, n = 50; NSCLC, n = 54) were employed to validate the prognostic value of candidate genes. A set of 1490 genes were identified in EMT model in vitro. An EMT-like gene-expression pattern by 33 essential genes was optimized in NSMs, and was significantly associated with tumor progression. The 33 genes also exhibited a site-dependent field cancerization effect in the normal-appearing airways adjacent to NSCLCs. In the independent lung SCC cohort, the EMT-like active pattern indicated poor outcome of patients (n = 50, log-rank p = 0.009). Furthermore, in the NSCLC cohort, patients with EMT-like active pattern had shorter predictive survival time (n = 54, log-rank p = 0.02). In conclusion, the existence of EMT-like gene expression in NSMs, may play critical role in tumor progression and be a potential biomarker for prognosis in patients with NSCLC.
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