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Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer

Authors Sun Y, Yu W, Guan W, Cai L, Qiao M, Zheng L, Jiang R, Wang R, Wang L

Received 21 February 2019

Accepted for publication 20 May 2019

Published 10 July 2019 Volume 2019:11 Pages 6397—6410

DOI https://doi.org/10.2147/CMAR.S206189

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Melinda Thomas

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Yeqi Sun,1,* Wenwei Yu,1,* Wenbin Guan,1,* Lei Cai,1 Meng Qiao,1 Leizhen Zheng,2 Ruiqi Jiang,1 Ruifen Wang,1 Lifeng Wang1

1Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, People’s Republic of China; 2Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, People’s Republic of China

*These authors contributed equally to this work

Purpose: Targeting the PD-1/PD-L1 pathway has emerged as a novel therapy for cancer. To identify rational candidates for anti-PD-1/PD-L1 immunotherapy in gastric cancer (GC), the abundance of PD-L1 expression was evaluated on a kind of biomarker-based molecular classification for shaping prognosis and treatment planning.
Methods: One hundred and sixty-five GCs were classified into five subgroups using immunohistochemistry (IHC) and in situ hybridization (ISH) methods, based on a panel of seven markers (MLH1, PMS2, MSH2, MSH6, E-cadherin, P53, and Epstein-Barr virus mRNA). The expression of PD-L1 in GC tissues was analyzed immunohistochemically.
Results: The five categories (Epstein–Barr virus positivity, microsatellite instability, aberrant E-cadherin, aberrant P53 expression, and normal P53 expression) correspond to the reported molecular subgroups for similar proportions and clinicopathologic characteristics. Survival analysis indicated that subgroups with aberrant E-cadherin expression independently predicted a worse prognosis in GC patients (HR=2.51, P=0.010). The clinical and prognostic profiles produced by this stratification in nonintestinal-type GC were distinguishable from those in intestinal-type. Although PD-L1 was not a significant prognostic factor, that more frequent presence of PD-L1-positive in microsatellite instability tumors than other subtypes (P<0.010) hinted at a prolonged clinical course. Moreover, the lowest level of PD-L1 but the highest of Her2 was observed in the group of aberrant P53, namely it was suggested that there was a negative correlation between PD-L1 and Her2 overexpression.
Conclusion: Different molecular subtypes in GC may have a tendency to react differently to anti-PD-L1/PD-1 immunotherapy or anti-Her2 therapy. A combination of PD-L1 expression and this cost-effective classification strategy would be helpful for predicting prognosis and promoting personalized therapy in clinical practice.

Keywords: PD-L1, molecular classification, gastric cancer, immunohistochemistry, in situ hybridization


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