title: An 8-gene signature for prediction of prognosis and chemoresponse in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.|Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department 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.
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Choi
authors.affiliation: Department 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.
authors.forename: Minh Nam
authors.initials: MN
authors.lastname: Nguyen
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Abel
authors.initials: A
authors.lastname: Matondo
authors.affiliation: Department 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.
authors.forename: Yong Hwa
authors.initials: YH
authors.lastname: Jo
authors.affiliation: Department 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.
authors.forename: Ji Youn
authors.initials: JY
authors.lastname: Yoo
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ngoc Ngo Yen
authors.initials: NN
authors.lastname: Nguyen
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyeong Rok
authors.initials: HR
authors.lastname: Yun
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department 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.
authors.forename: Salima
authors.initials: S
authors.lastname: Akter
authors.affiliation: Department 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.
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department 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.
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.affiliation: Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea.
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Maeng
authors.affiliation: Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea.
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department 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.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D059467:Transcriptome
chemical_list: C117307:KRAS protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: chemosensitivity; microarray analysis; non-small cell lung cancer; prognosis