A 5-microRNA signature identified from serum microRNA profiling predicts survival in patients with advanced stage non-small cell lung cancer

Yajie Zhang, Jack A. Roth, Hao Yu, Yuanqing Ye, Kunlin Xie, Hua Zhao, David W. Chang, Maosheng Huang, Hecheng Li, Jieming Qu, Xifeng Wu

Research output: Contribution to journalArticle

Abstract

Circulating microRNAs (miRNAs) are potential biomarkers for cancer diagnosis, screening and prognosis. This study aimed to identify serum miRNAs as predictors of survival in patients with advanced non-small cell lung cancer (NSCLC). We profiled serum miRNAs in a pilot set of four patients with good survival (>24 months) and four patients with poor survival (<6 months). We selected 140 stably detectable miRNAs and 42 miRNAs reported in literature for further analysis. Expression of these 182 miRNAs was measured using high-throughput polymerase chain reaction assay, and their association with 3-year survival in the discovery (n = 345) and validation (n = 177) cohorts was assessed. Five serum miRNAs (miR-191, miR-28-3p, miR-145, miR-328 and miR-18a) were significantly associated with 3-year overall survival in both cohorts. A combined 5-miRNA risk score was created to assess the cumulative impact of these miRNAs on risk of death. Quartile analysis of the risk score showed significant association with 3-year death risk, with a 4.6-, 6.8- and 9.3-month reduction in median survival time for the second, third and fourth quartiles, respectively. Survival tree analysis also identified distinct risk groups with different 3-year survival durations. Data from The Cancer Genome Atlas revealed all five miRNAs were differentially expressed (P < 0.0001) in paired tumor and normal tissues. Pathway analysis indicated that target genes of these five miRNAs were mainly enriched in inflammatory/immune response pathways and pathways implicated in resistance to chemoradiotherapy and/or targeted therapy. Our results suggested that the 5-miRNA signature could serve as a prognostic predictor in patients with advanced NSCLC.

Original languageEnglish (US)
Pages (from-to)643-650
Number of pages8
JournalCarcinogenesis
Volume40
Issue number5
DOIs
StatePublished - Jul 4 2019

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MicroRNAs
Non-Small Cell Lung Carcinoma
Survival
Serum
Atlases
Chemoradiotherapy
Survival Analysis
Early Detection of Cancer
Neoplasms
Biomarkers
Genome
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research

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A 5-microRNA signature identified from serum microRNA profiling predicts survival in patients with advanced stage non-small cell lung cancer. / Zhang, Yajie; Roth, Jack A.; Yu, Hao; Ye, Yuanqing; Xie, Kunlin; Zhao, Hua; Chang, David W.; Huang, Maosheng; Li, Hecheng; Qu, Jieming; Wu, Xifeng.

In: Carcinogenesis, Vol. 40, No. 5, 04.07.2019, p. 643-650.

Research output: Contribution to journalArticle

Zhang, Y, Roth, JA, Yu, H, Ye, Y, Xie, K, Zhao, H, Chang, DW, Huang, M, Li, H, Qu, J & Wu, X 2019, 'A 5-microRNA signature identified from serum microRNA profiling predicts survival in patients with advanced stage non-small cell lung cancer', Carcinogenesis, vol. 40, no. 5, pp. 643-650. https://doi.org/10.1093/carcin/bgy132
Zhang, Yajie ; Roth, Jack A. ; Yu, Hao ; Ye, Yuanqing ; Xie, Kunlin ; Zhao, Hua ; Chang, David W. ; Huang, Maosheng ; Li, Hecheng ; Qu, Jieming ; Wu, Xifeng. / A 5-microRNA signature identified from serum microRNA profiling predicts survival in patients with advanced stage non-small cell lung cancer. In: Carcinogenesis. 2019 ; Vol. 40, No. 5. pp. 643-650.
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AU - Chang, David W.

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AB - Circulating microRNAs (miRNAs) are potential biomarkers for cancer diagnosis, screening and prognosis. This study aimed to identify serum miRNAs as predictors of survival in patients with advanced non-small cell lung cancer (NSCLC). We profiled serum miRNAs in a pilot set of four patients with good survival (>24 months) and four patients with poor survival (<6 months). We selected 140 stably detectable miRNAs and 42 miRNAs reported in literature for further analysis. Expression of these 182 miRNAs was measured using high-throughput polymerase chain reaction assay, and their association with 3-year survival in the discovery (n = 345) and validation (n = 177) cohorts was assessed. Five serum miRNAs (miR-191, miR-28-3p, miR-145, miR-328 and miR-18a) were significantly associated with 3-year overall survival in both cohorts. A combined 5-miRNA risk score was created to assess the cumulative impact of these miRNAs on risk of death. Quartile analysis of the risk score showed significant association with 3-year death risk, with a 4.6-, 6.8- and 9.3-month reduction in median survival time for the second, third and fourth quartiles, respectively. Survival tree analysis also identified distinct risk groups with different 3-year survival durations. Data from The Cancer Genome Atlas revealed all five miRNAs were differentially expressed (P < 0.0001) in paired tumor and normal tissues. Pathway analysis indicated that target genes of these five miRNAs were mainly enriched in inflammatory/immune response pathways and pathways implicated in resistance to chemoradiotherapy and/or targeted therapy. Our results suggested that the 5-miRNA signature could serve as a prognostic predictor in patients with advanced NSCLC.

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