An 8-gene signature for prediction of prognosis and chemoresponse in non-small cell lung cancer
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Muhammad Shahid1,5,*, Tae Gyu Choi2,*, Minh Nam Nguyen2, Abel Matondo1, Yong Hwa Jo2, Ji Youn Yoo2, Ngoc Ngo Yen Nguyen1, Hyeong Rok Yun1, Jieun Kim1, Salima Akter2, Insug Kang2, Joohun Ha2, Chi Hoon Maeng3, Si-Young Kim3, Ju-seog Lee4, Jayoung Kim5, Sung Soo Kim2
1Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea
2Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
3Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea
4Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
5Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
*These authors have contributed equally to this work
Sung Soo Kim, email: [email protected]
Keywords: non-small cell lung cancer, microarray analysis, prognosis, chemosensitivity
Received: October 04, 2016 Accepted: October 29, 2016 Published: November 15, 2016
Identification of a potential gene signature for improved diagnosis in non-small cell lung cancer (NSCLC) patient is necessary. Here, we aim to establish and validate the prognostic efficacy of a gene set that can predict prognosis and benefits of adjuvant chemotherapy (ACT) in NSCLC patients from various ethnicities. An 8-gene signature was calculated from the gene expression of 181 patients using univariate Cox proportional hazard regression analysis. The prognostic value of the signature was robustly validated in 1,477 patients from five microarray independent data sets and one RNA-seq data set. The 8-gene signature was identified as an independent predictor of patient survival in the presence of clinical parameters in univariate and multivariate analyses [hazard ratio (HR): 2.84, 95% confidence interval CI (1.74-4.65), p=3.06e-05, [HR] 2.62, 95% CI (1.51-4.53), p=0.001], respectively. Subset analysis demonstrated that the 8-gene signature could identify high-risk patients in stage II-III with improved survival from ACT [(HR) 1.47, 95% CI (1.01-2.14), p=0.044]. The 8-gene signature also stratified risk groups in EGFR-mutated and wild-type patients. In conclusion, the 8-gene signature is a strong and independent predictor that can significantly stratify patients into low- and high-risk groups. Our gene signature also has the potential to predict patients in stage II-III that are likely to benefit from ACT.
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