CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer.
OBJECTIVE
Lung cancer is a heterogeneous disease with varied outcomes. Molecular markers are eagerly investigated to predict a patient's treatment response or outcome. Previous studies used frozen biopsy tissues to identify crucial genes as prognostic markers. We explored the prognostic value of peripheral blood (PB) molecular signatures in patients with advanced non-small cell lung cancer (NSCLC).


METHODS
Peripheral blood mononuclear cell (PBMC) fractions from patients with advanced NSCLC were applied for RNA extraction, cDNA synthesis, and real-time polymerase chain reaction (PCR) for the expression profiling of eight genes: DUSP6, MMD, CPEB4, RNF4, STAT2, NF1, IRF4, and ZNF264. Proportional hazard (PH) models were constructed to evaluate the association of the eight expressing genes and multiple clinical factors [e.g., sex, smoking status, and Charlson comorbidity index (CCI)] with overall survival.


RESULTS
One hundred and forty-one patients with advanced NSCLC were enrolled. They included 109 (77.30%) patients with adenocarcinoma, 12 (8.51%) patients with squamous cell carcinoma, and 20 (14.18%) patients with other pathological lung cancer types. A PH model containing two significant survival-associated genes, CPEB4 and IRF4, could help in predicting the overall survival of patients with advanced stage NSCLC [hazard ratio (HR) = 0.48, p < 0.0001). Adding multiple clinical factors further improved the prediction power of prognosis (HR = 0.33; p < 0.0001).


CONCLUSIONS
Molecular signatures in PB can stratify the prognosis in patients with advanced NSCLC. Further prospective, interventional clinical trials should be performed to test if gene profiling also predicts resistance to chemotherapy.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Yi-Ying
YY
Wu
Department of Statistics, National Taipei University, New Taipei City, Taiwan.
Yi-Ting
YT
Hwang
Division of Pulmonary Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Wann-Cherng
WC
Perng
Division of Pulmonary Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Chih-Feng
CF
Chian
Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Ching-Liang
CL
Ho
Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital National, Taipei, Taiwan.
Shih-Chun
SC
Lee
Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital National, Taipei, Taiwan.
Hung
H
Chang
Advpharma, Inc., New Taipei City, Taiwan.
Harn-Jing
HJ
Terng
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. Electronic address: 10575@s.tmu.edu.tw.
Tsu-Yi
TY
Chao
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality*; D004358:Drug Therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D013624:Taiwan; D000099218:Interferon Regulatory Factor-4
D014408:Biomarkers, Tumor; D050835:Interferon Regulatory Factors; D016601:RNA-Binding Proteins; D000099218:Interferon Regulatory Factor-4; C554939:CPEB4 protein, human
lung neoplasms; peripheral blood mononuclear cell; survival