Prognostic and Predictive Value of p21-activated Kinase 6 Associated Support Vector Machine Classifier in Gastric Cancer Treated by 5-fluorouracil/Oxaliplatin Chemotherapy

EBioMedicine

Shirong Cai¹  Sile Chen¹  Zhen Han²  Liying Zhao²  Yanfeng Hu²  Jiang Yu²  Xiaolong Qi²  Yuming Jiang²  Tuanjie Li²  Guoxin Li²  Hao Liu²  Lei Huang³  Yang Yang⁴  Sujuan Xi⁴  Wei Liu⁴  Yajia Wen⁴  Cuicui Xiao⁴  Xiaohui Huang⁴ 

[1] Department of Gastrointestinal Surgery of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, Guangdong, China;Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China;German Cancer Research Center (DKFZ), Heidelberg 69120, Germany;Guangdong Key Laboratory of Liver Disease Research, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China;

关键词: Gastric cancer;    p21-activated kinase 6;    5-FU/oxaliplatin chemotherapy;    SVM classifier;    Nomogram;   

DOI  :  10.1016/j.ebiom.2017.06.028

来源: DOAJ

【 摘 要 】

To determine whether p21-activated Kinase (PAK) 6 is a prognostic and predictive marker in gastric cancer (GC) and to construct a classifier that can identify a subset of patients who are highly sensitive to 5-fluorouracil/oxaliplatin chemotherapy. We retrospectively analyzed the expression levels of PAK6, cyclooxygenase 2, p21WAF1, Ki-67, excision repair cross-complementing gene 1, and thymidylate synthase in 242 paraffin-embedded GC specimens of the training cohort by immunohistochemistry. Then, we used support vector machine (SVM)–based methods to develop a predictive classifier for chemotherapy (chemotherapy score – CS-SVM classifier). Further validation was performed in an independent cohort of 279 patients. High PAK6 expression was associated with poor prognosis and increased chemoresistance to 5-FU/oxaliplatin chemotherapy. The CS-SVM classifier distinguished patients with stage II and III GC into low- and high-CS-SVM groups, with significant differences in the 5-year disease-free survival (DFS) and overall survival (OS) in chemotherapy patients. Moreover, chemotherapy significantly prolonged the DFS and OS of the high CS-SVM patients in the training and validation cohorts. In conclusion, PAK6 was an independent prognostic factor and increased chemoresistance. The CS-SVM classifier distinguished a subgroup of stage II and III patients who would highly benefit from chemotherapy, thus facilitating patient counseling and individualizing the management.

【 授权许可】

Unknown