Affiliations: [a] Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan | [b] Biostatistics and Bioinformatics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA | [c] Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA | [d] Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA | [e] Department of Surgery, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Correspondence:
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Corresponding authors: Y. Peng Loh, Bldg. 49, Rm. 6A-10, National Institutes of Health, 49, Convent Drive, Bethesda, Md. 20892, USA. E-mail: lohp@mail.nih.gov. Yi-Ching Wang, Institute of Basic Medical Sciences and Department Pharmacology, National Cheng Kung University, No.1, University Road, Tainan 70101, Taiwan. E-mail: ycw5798@mail.ncku.edu.tw.
Abstract: BACKGROUND: Effective biomarkers for prediction of recurrence of lung adenocarcinoma cancer (LADC) patients are needed to determine treatment strategies post-surgery to improve outcome. OBJECTIVE: This study evaluates the efficacy of carboxypeptidase E (CPE) mRNA including its splice isoforms, CPE-ΔN, as a biomarker for predicting recurrence in adenocarcinoma patients. METHODS:RNA was extracted from resected tumors from 86 patients with different stages of non-small cell LADC. cDNA was synthesized and qRT-PCR carried out to determine the copy numbers of CPE/CPE-ΔN mRNA. Patients were followed for 7 years post-tumor resection to determine recurrence and death. RESULTS: ROC curve analysis showed the overall AUC for CPE/CPE-ΔN copy number was 0.563 in predicting recurrence and 0.562 in predicting death. Kaplan-Meier survival analysis showed statistical difference (p= 0.018), indicating that patients with high CPE/CPE-ΔN copy numbers had a shorter time of disease-free survival and also shorter time to death (p= 0.035). Subgroup analyses showed that association of disease-free survival time with CPE/CPE-ΔN copy number was stronger among stage I and II LADC patients (p= 0.047). CONCLUSIONS:CPE/CPE-ΔN mRNA is a potentially useful biomarker for predicting recurrence and death in LADC patients, especially in identifying patients at high risk of recurrence at early stages I and II.
Keywords: Lung cancer, carboxypeptidase E, cancer biomarker, adenocarcinoma
