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EBioMedicine. 2017 Aug;22:78-88. doi: 10.1016/j.ebiom.2017.06.028. Epub 2017 Jul 1.

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

Author information

1
Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China; Guangdong Key Laboratory of Liver Disease Research, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
2
Guangdong Key Laboratory of Liver Disease Research, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Department of Hepatic Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
3
Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China.
4
Department of Gastrointestinal Surgery of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, Guangdong, China.
5
Guangdong Key Laboratory of Liver Disease Research, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Department of Infectious disease, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
6
German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
7
Guangdong Key Laboratory of Liver Disease Research, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
8
Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China. Electronic address: balbc@163.com.
9
Department of Gastrointestinal Surgery of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, Guangdong, China. Electronic address: caishirong@yeah.net.
10
Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China. Electronic address: gzliguoxin@163.com.

Abstract

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.

KEYWORDS:

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

PMID:
28687498
PMCID:
PMC5552213
DOI:
10.1016/j.ebiom.2017.06.028
[Indexed for MEDLINE]
Free PMC Article

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