title: Expression and prognostic roles of PIK3CA, JAK2, PD-L1, and PD-L2 in Epstein-Barr virus-associated gastric carcinoma.
abstract: As a special subtype of gastric carcinoma, Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. The Cancer Genome Atlas Research Network revealed that EBVaGC also has distinct molecular features: PIK3CA mutations, DNA hypermethylation, and JAK2, PD-L1, and PD-L2 amplification. Here, we evaluated PIK3CA, JAK2, PD-L1, and PD-L2 expression in 59 EBVaGC and 796 EBV-negative gastric carcinoma (EBVnGC) cases using immunohistochemistry and found that PIK3CA, JAK2, PD-L1, and PD-L2 were highly expressed in 75.9% and 48.8% (P<.001), 81.8% and 71.1% (P=.091), 92.5% and 84.8% (P=.132), and 98.1% and 89.7% (P=.049) of the EBVaGC and EBVnGC cases, respectively. However, the expression of PIK3CA, JAK2, PD-L1, or PD-L2 was not significantly associated with clinicopathological features or patient outcomes in EBVaGC. In contrast, in EBVnGC, high PIK3CA expression was significantly associated with indolent clinicopathological features and independently predicted better 5-year overall survival (57.8% versus 33.4%, P<.001). Our study indicated that the protein expression of the 4 characteristic molecules of EBVaGC was basically consistent with their genetic alterations, making them potential characteristic protein biomarkers and therapeutic targets of EBVaGC. The favorable impact of PIK3CA overexpression on survival found in this study gives us new insight into the clinical significance of PIK3CA in EBVnGC.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Pathology and Institute of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; Department of Pathology, Wuhan Central Hospital, Wuhan 430014, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Zhao
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Yi-Wang
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Li
authors.affiliation: Department of Pathology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. Electronic address: chunkuishao2011@163.com.
authors.forename: Chun-Kui
authors.initials: CK
authors.lastname: Shao
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000821:virology; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D016009:Chi-Square Distribution; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053614:Janus Kinase 2 / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000032:analysis*; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000821:virology
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D004279:DNA, Viral; C099537:Epstein-Barr virus encoded RNA 1; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012367:RNA, Viral; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: EBVaGC; JAK2; PD-L1; PD-L2; PIK3CA