CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer

Yi Ying Wu, Yi Ting Hwang, Wann Cherng Perng, Chih Feng Chian, Ching Liang Ho, Shih Chun Lee, Hung Chang, Harn Jing Terng, Tsu Yi Chao

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background/Purpose: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)114-122
JournalJournal of the Formosan Medical Association
Volume116
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

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Lung Neoplasms
Non-Small Cell Lung Carcinoma
Proportional Hazards Models
Genes
Survival
Sex Factors
Gene Expression Profiling
Comorbidity
Real-Time Polymerase Chain Reaction
Squamous Cell Carcinoma
Blood Cells
Adenocarcinoma
Complementary DNA
Smoking
Clinical Trials
RNA
Biopsy
Drug Therapy

Keywords

  • Lung neoplasms
  • Peripheral blood mononuclear cell
  • Survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer. / Wu, Yi Ying; Hwang, Yi Ting; Perng, Wann Cherng; Chian, Chih Feng; Ho, Ching Liang; Lee, Shih Chun; Chang, Hung; Terng, Harn Jing; Chao, Tsu Yi.

In: Journal of the Formosan Medical Association, Vol. 116, No. 2, 01.02.2017, p. 114-122.

Research output: Contribution to journalArticle

Wu, Yi Ying ; Hwang, Yi Ting ; Perng, Wann Cherng ; Chian, Chih Feng ; Ho, Ching Liang ; Lee, Shih Chun ; Chang, Hung ; Terng, Harn Jing ; Chao, Tsu Yi. / CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer. In: Journal of the Formosan Medical Association. 2017 ; Vol. 116, No. 2. pp. 114-122.
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T1 - CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer

AU - Wu, Yi Ying

AU - Hwang, Yi Ting

AU - Perng, Wann Cherng

AU - Chian, Chih Feng

AU - Ho, Ching Liang

AU - Lee, Shih Chun

AU - Chang, Hung

AU - Terng, Harn Jing

AU - Chao, Tsu Yi

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Y1 - 2017/2/1

N2 - Background/Purpose: 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). Conclusion: 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.

AB - Background/Purpose: 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). Conclusion: 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.

KW - Lung neoplasms

KW - Peripheral blood mononuclear cell

KW - Survival

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