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Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

ABSTRACT: In this study, we conducted a meta-analysis on high-throughput gene expression data to identify TNF-?-mediated genes implicated in lung cancer. We first investigated the gene expression profiles of two independent TNF-?/TNFR KO murine models. The EGF receptor signaling pathway was the top pathway associated with genes mediated by TNF-?. After matching the TNF-?-mediated mouse genes to their human orthologs, we compared the expression patterns of the TNF-?-mediated genes in normal and tumor lung tissues obtained from humans. Based on the TNF-?-mediated genes that were dysregulated in lung tumors, we developed a prognostic gene signature that effectively predicted recurrence-free survival in lung cancer in two validation cohorts. Resampling tests suggested that the prognostic power of the gene signature was not by chance, and multivariate analysis suggested that this gene signature was independent of the traditional clinical factors and enhanced the identification of lung cancer patients at greater risk for recurrence.

SUBMITTER: Wang B

PROVIDER: S-EPMC4280165 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

Wang Baohua B Song Ning N Yu Tong T Zhou Lianya L Zhang Helin H Duan Lin L He Wenshu W Zhu Yihua Y Bai Yunfei Y Zhu Miao M

PloS one 20141230 12

In this study, we conducted a meta-analysis on high-throughput gene expression data to identify TNF-α-mediated genes implicated in lung cancer. We first investigated the gene expression profiles of two independent TNF-α/TNFR KO murine models. The EGF receptor signaling pathway was the top pathway associated with genes mediated by TNF-α. After matching the TNF-α-mediated mouse genes to their human orthologs, we compared the expression patterns of the TNF-α-mediated genes in normal and tumor lung ...[more]

PMID: 25548907

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Project description:BackgroundThere is currently a lack of effective biomarkers to evaluate efficacy of neoadjuvant therapy (NAT) for resectable non-small cell lung cancer (NSCLC) patients. Circulating tumor DNA (ctDNA) has been investigated as a non-invasive tool for the assessment of tumor burden and minimal residual disease (MRD). The utility of ctDNA profiling in reflecting NAT efficacy, however, has not been confirmed. This study explored the association of ctDNA change with treatment response to NAT and recurrence-free survival (RFS) after surgery.MethodsEligible patients with stage IB-IIIA NSCLC were retrospectively included if they had received neoadjuvant immunotherapy combined with chemotherapy (IO+Chemo), dual immunotherapy (IO+IO), or chemotherapy alone (Chemo). We conducted ctDNA profiling before and after NAT, after surgery, and during follow-ups using an ultra-deep lung cancer-specific MRD (LC-MRD) sequencing panel.ResultsA total of 22 patients who received NAT followed by surgery between August 2018 and July 2019 were included in this study. The major pathological response (MPR) rates were 58.33% (7/12) in the IO+Chemo group, 25.00% (1/4) in the IO+IO group, and 16.67% (1/6) in the Chemo group. The ctDNA dynamics during NAT were highly concordant with pathologic response, demonstrating 100% sensitivity and 83.33% specificity, for an overall accuracy of 91.67%. Pre-surgery detectable ctDNA (after NAT) trended to correlate with inferior RFS [hazard ratio (HR), 7.41; 95% confidence interval (CI): 0.91-60.22, log-rank P=0.03]. At 3-8 days after surgery, ctDNA was detectable in 31.8% of patients and was an independent risk factor for recurrence (HR, 5.37; 95% CI: 1.27-22.67; log-rank P=0.01). The presence of ctDNA at 3 months after surgery showed 83% sensitivity and 90% specificity for predicting relapse (C-index, 0.79; 95% CI: 0.62-0.95). During disease monitoring after surgery, molecular recurrence by means of ctDNA preceded radiographic relapse, with a median time of 6.83 months.ConclusionsThis study investigated the potential of ctDNA in evaluating NAT efficacy in NSCLC, implying the high concordance between ctDNA and pathological response. We also set out the prognostic value of perioperative ctDNA in predicting recurrence.

Dataset Information

Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

Publications

Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

Similar Datasets

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