Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Zhang, Li; Wu, Aiwen; Li, Zhongwu

doi:10.21203/rs.3.rs-48875/v3

Cited by 3 publications

(3 citation statements)

References 37 publications

(38 reference statements)

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“…The mutation of the DDR gene in cancer cells is usually associated with the increased expression of PD-1/ PD-L1 genes within the TME [56,64,233,234], such as the DSB repair gene [221], MMR gene [146,235,236] and RB1 [171,237]. The expression of BER/SSBR has been shown to be negatively correlated with the level of PD-L1 observed in cancer cells [150,235].…”

Section: Abnormal Ddr Pathway and Immune Checkpoint Moleculesmentioning

confidence: 99%

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Shi

Qin

Lin

et al. 2022

J Exp Clin Cancer Res

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As our understanding of the mechanisms of cancer treatment has increased, a growing number of studies demonstrate pathways through which DNA damage repair (DDR) affects the immune system. At the same time, the varied response of patients to immune checkpoint blockade (ICB) therapy has prompted the discovery of various predictive biomarkers and the study of combination therapy. Here, our investigation explores the interactions involved in combination therapy, accompanied by a review that summarizes currently identified and promising predictors of response to immune checkpoint inhibitors (ICIs) that are useful for classifying oncology patients. In addition, this work, which discusses immunogenicity and several components of the tumor immune microenvironment, serves to illustrate the mechanism by which higher response rates and improved efficacy of DDR inhibitors (DDRi) in combination with ICIs are achieved.

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Section: Abnormal Ddr Pathway and Immune Checkpoint Moleculesmentioning

confidence: 99%

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Shi

Qin

Lin

et al. 2022

J Exp Clin Cancer Res

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“…Therefore, in intestinal-type neoplasms of the vulva, a gene panel test may be helpful to select treatment options. In addition, while present case was microsatellite stable, some reports have shown that microsatellite instability-high and mismatch repair deficiency is more frequent in gastric adenocarcinoma of intestinal-type [54,55], and microsatellite status and IHC for mismatch repair protein may also be checked in intestinal-type neoplasms of the vulva.…”

Section: Discussionmentioning

confidence: 51%

Tubulovillous adenoma with high-grade dysplasia of the vulva harboring high tumor mutational burden and cancer-associated mutations: a case report

et al. 2022

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Background Vulvar cancer is a rare disease, accounting for approximately 5% of gynecological malignancies. Primary adenocarcinoma of intestinal-type of the vulva or its precancerous lesion is extremely rare, and details regarding its origin, evolution and related genetic mutations are unknown. Treatment options for this cancer have not been defined. Case presentation A 63-year-old Japanese woman came to the hospital because she was aware of a vulvar mass. There was a 1 cm mass on the dorsal side of the vulva, just outside the remains of the hymen. Biopsy revealed suspected adenocarcinoma, and wide local excision was performed. From histopathology and immunohistochemistry, the specimen was diagnosed as tubulovillous adenoma with high-grade dysplasia of the vulva. No other primary lesions were found, and the vulva was considered the primary site. A gene panel test (FoundationOneCDx assay) showed a high tumor mutational burden and mutations in TP53, KEL, RB1, RNF43, PTEN, GNAS, and PIK3CA. Conclusions The current case of tubulovillous adenoma with high-grade dysplasia of the vulva had a variety of cancer-associated mutations, despite being a precancerous lesion. In cases of intestinal-type neoplasms of the vulva, it may be helpful to check tumor mutational burden and gene mutations for treatment selection.

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“…Kakiuchi et al, 25 Birkman et al, 60 Machado et al 73 RhoA Mt (0%) Mt (15-25%) Cancer Genome Atlas Research Network, 18 Kakiuchi et al, 25 Wang et al 74 ARID1A Mt (12-16%) Mt (9-15%) Kakiuchi et al, 25 Wu et al, 75 Garcia-Pelaez et al 76 Claudin 18.2 OverExp (15-46%) OverExp (28-75%) Sahin et al, 77 Dottermusch et al, 78 Pellino et al, 79 Coati et al 80 MSI-H /dMMR 4-10% 0-4% Kim et al, 55 Birkman et al, 60 Zhang et al 81 EBV 1-9% 0-4% Kim et al, 55 Birkman et al, 60 Zhang et al 81 PD-L1* OverExp (28-65%) OverExp (19-54%) Fukamachi et al, 82 Liu et al, 83 CDH1 is a tumor suppressor gene that codes for E-cadherin, which is a calcium-dependent transmembrane glycoprotein that forms the adherens junction via the extracellular domains, connects to the cytoskeleton via the cytoplasmic domains, and mediates cellular signaling. 85 Loss of its function confers diffused cellular morphology, migratory and invasive abilities, metastasis, and the EMT process.…”

Section: Cdh1mentioning

confidence: 99%

The dawn of precision medicine in diffuse-type gastric cancer

Ooki

Yamaguchi

2022

Ther Adv Med Oncol

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Gastric cancer (GC) is one of the most common malignancies worldwide. The histology- and morphology-based Lauren classification of GC has been widely used for over 50 years in clinical practice. The Lauren classification divides GC into intestinal and diffuse types, which have distinct etiology, molecular profiles, and clinicopathological features. Diffuse-type GC (DGC) accounts for approximately 30% of GCs. Tumor cells lack adhesion and infiltrate the stroma as single cells or small subgroups, leading to easy dissemination in the abdominal cavity. Clinically, DGC has aggressive traits with a high risk of recurrence and metastasis, which results in unfavorable prognosis. Although systemic chemotherapy is the main therapeutic approach for recurrent or metastatic GC patients, clinical benefits are limited for patients with DGC. Therefore, it is urgent to develop effective therapeutic strategies for DGC patients. Considerable research studies have characterized the molecular and genomic landscape of DGC, of which tight junction protein claudin-18 isoform 2 (CLDN18.2) and fibroblast growing factors receptor-2 isoform IIIb (FGFR2-IIIb) are the most attractive targets because of their close association with DGC. Recently, the impressive results of two phase II FAST and FIGHT trials demonstrate proof-of-concept, suggesting that anti-CLDN18.2 antibody (zolbetuximab) and FGFR2-IIIb antibody (bemarituzumab) are promising approaches for patients with CLDN18.2-positive and FGFR2-IIIb-positive GC, respectively. In this review, we summarize the clinicopathological features and molecular profiles of DGC and highlight a potential therapeutic target based on the findings of pivotal clinical trials.

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Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Cited by 3 publications

References 37 publications

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Tubulovillous adenoma with high-grade dysplasia of the vulva harboring high tumor mutational burden and cancer-associated mutations: a case report

The dawn of precision medicine in diffuse-type gastric cancer

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