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Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer.

ABSTRACT: 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.

SUBMITTER: Cao B

PROVIDER: S-EPMC5581137 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer.

Cao Bangrong B Feng Lin L Lu Dan D Liu Yan Y Liu Yu Y Guo Suping S Han Naijun N Liu Xiangyang X Mao Yousheng Y He Jie J Cheng Shujun S Gao Yanning Y Zhang Kaitai K

Oncotarget 20160729 32

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 carcino ...[more]

PMID: 28881838

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Project description:BACKGROUND:Incomplete lung cancer resection connotes poor prognosis; the incidence varies with patient demographic, clinical, and institutional factors. We sought to develop a valid, survival impactful, facility-based surgical quality metric that adjusts for related patient demographic and clinical characteristics. METHODS:Facilities performing resections for patients diagnosed with stage I to IIIA non-small cell lung cancer in the National Cancer Data Base between 2004 and 2011 were identified. Multivariate logistic regression modeling was used to estimate the expected number of margin-positive cases by adjusting for patient risk mix and calculate the observed-to-expected ratio for each facility. Facilities were categorized as outperformers (observed-to-expected ratio less than 1, p < 0.05), nonoutliers (p > 0.05), and underperformers (observed-to-expected ratio greater than 1, p < 0.05); and their characteristics across performance categories were compared by ?2 tests. Multivariate Cox proportional hazard analyses were conducted, adjusting for patient demographic and clinical characteristics. RESULTS:A total of 96,324 patients underwent surgery at 809 facilities. The overall observed margin-positive rate was 4.4%. Sixty-one facilities (8%) were outperformers, 644 (80%) were nonoutliers, and 104 (13%) were underperformers. One third (36%) of National Cancer Institute-designated facilities, 13% of academic comprehensive cancer programs, 5% of comprehensive community cancer programs, and 13% of "other" facilities achieved outperforming status but no community cancer programs did. Interestingly, 9% of National Cancer Institute-designated facilities and 11% of academic comprehensive cancer program facilities were underperformers. Adjusting for patient demographic and clinical characteristics, outperformers had a 5-year all-cause hazard ratio of 0.88 (95% confidence interval: 0.85 to 0.91, p < 0.0001) compared with nonoutliers, and 0.80 (95% confidence interval: 0.77 to 0.84, p < 0.0001) compared with underperformers. CONCLUSIONS:Facility performance in lung cancer surgery can be captured by the risk-adjusted margin-positivity rate, potentially providing a valid quality improvement metric.

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Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer.

Publications

Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer.

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