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

Abstract

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.

CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma

“…Nevertheless, most of patients fail to respond to PD-1/PD-L1 axis inhibitors. The abnormal expression of PD-L1 can be used as a predictive or prognostic marker of PD-1/PD-L1 inhibition therapy for patients (31)(32)(33). However, few studies have studied the expression and regulatory mechanisms of PD-1 or PD-L1 expression in T-LBL (34,35).…”

CircRNA_0005075 suppresses carcinogenesis via regulating miR‐431/p53/epithelial‐mesenchymal transition axis in gastric cancer

“…1,2 Recently, the treatment for the post-operated GC patients, including molecule-targeted therapy and immunotherapy, had made a big through. 15,16 However, due to the lack of the typical symptoms and effectively screening methods in the early stage, numerous patients were diagnosed with advanced GC and their 5-year survival rate was not satisfactory. Interestingly, based on the high-through put sequencing and bioinformatics technologies, increasing attention had been paid for verifying the biological role of CircRNAs in the development of GC.…”

“…GC is one of the most common malignant tumours in the world . Recently, the treatment for the post‐operated GC patients, including molecule‐targeted therapy and immunotherapy, had made a big through . However, due to the lack of the typical symptoms and effectively screening methods in the early stage, numerous patients were diagnosed with advanced GC and their 5‐year survival rate was not satisfactory.…”

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

“…In the present study, the estimated EBV positive rate was 11.3%. EBV positive rates ranged from 1.2% to 89.2% in the individual eligible studies [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

“…In previous studies, EBV positivity has been significantly correlated with some clinicopathological characteristics, sex, and tumor location [ 22 , 26 , 53 ]. In the present study, there was a significant correlation between EBV positivity and the patient’s sex; however, EBV positivity was not correlated with lymphovascular invasion or pTNM stage.…”