Claudins and Gastric Cancer: An Overview

Hashimoto, Itaru; Oshima, Takashi

doi:10.3390/cancers14020290

Cited by 69 publications

(62 citation statements)

References 129 publications

(178 reference statements)

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“…EMT and gastric cancer stem cells underlie the development of metastasis in gastric cancer and are important causes of refractory and recurrent gastric cancer (37,51). Our study revealed that NPRL2 might regulate the malignant biological behaviour of gastric cancer by affecting the EMT regulators and stemness of cells, which was consistent with Ji et al's study in lung cancer (8), where NPRL2 was able to inhibit the growth and metastasis of cancer cells.…”

Section: Discussionsupporting

confidence: 91%

Bioinformatics analysis of the prognostic and immunotherapeutic significance of NPRL2 in stomach adenocarcinoma

Pi¹,

Zhan²,

Song³

et al. 2022

J Gastrointest Oncol

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Background: Stomach adenocarcinoma (STAD) is a major type of gastric cancer with high morbidity and mortality. NPRL2, a candidate cancer suppressor gene, has been shown to have anti-cancer effects in various types of cancers. Therefore, comprehensive analyses of NPRL2 in STAD may provide a potential prognostic marker and clinical target for the management of gastric cancer.Methods: Genomic expression and methylation were analysed based on data from the Human Protein Atlas, Gene Expression Omnibus and Oncomine database. Survival analyses were conducted with the Kaplan-Meier method, using data from The Cancer Genome Atlas database. Immune correlation analyses and prediction of response to immunotherapy were performed using the online Immune Cell Abundance Identifier. Co-expression analyses, functional clustering analyses and construction of a prognostic risk model were conducted in R, with the clinical covariates balanced by the inverse probability treatment weighting method.Results: NPRL2 was abnormally downregulated in STAD (P<0.05). Survival analysis highlighted a positive association between the expression of NPRL2 and clinical outcomes for patients (P<0.05). Based on co-expression analyses, we found that NPRL2 may be involved in epithelial-mesenchymal transition, gastric cancer stem cells, and responsiveness to chemotherapeutic agents in STAD (P<0.05). Furthermore, functional clustering analysis revealed that NPRL2 was involved in the mTOR signalling pathway, autophagy, and the amino acid starvation response (adjust P<0.05). In addition, NPRL2 was negatively associated with tumour-infiltrating immune cells while positively associated with immunotherapeutic biomarkers in STAD (P<0.05). Meanwhile, patients with high NPRL2 expression were predicted to have a better response to immunotherapy (P<0.05). Finally, a prognostic model constructed based on NPRL2-related genes could predict the prognosis of STAD patients (AUC =0.641), and the risk score was an independent prognostic factor for STAD patients (HR =4.855, 95% CI: 2.683-8.785, P<0.001). Conclusions:The present study provided a comprehensive analysis of the role and potential mechanisms of NPRL2 in STAD, suggesting that NPRL2 is a potential biomarker for the survival and prediction of immunotherapy response in STAD.

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Section: Discussionsupporting

confidence: 91%

Bioinformatics analysis of the prognostic and immunotherapeutic significance of NPRL2 in stomach adenocarcinoma

Pi¹,

Zhan²,

Song³

et al. 2022

J Gastrointest Oncol

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“…RhoA signaling is crucial for two clinical aspects [ 5 , 38 , 39 ]: (1) possible biomarkers and (2) therapeutic target possibilities, based on the aforementioned functional roles of RHOA and our meta-analysis findings. Meta-analyses can provide insights for the usage of RHOA for patient classification.…”

Section: Discussionmentioning

confidence: 99%

RHOA protein expression correlates with clinical features in gastric cancer: a systematic review and meta-analysis

2022

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Background Gastric cancer (GC) is one of the most fatal cancers worldwide and is generally only detected after it has progressed to an advanced stage. Since there is a lack of comprehensive data on RHOA protein expression of patients with GC, this study utilized a systematic review and meta-analysis to address the limitation. The objective of this meta-analysis was to link GC clinical features with RHOA protein high- vs. low-expressing patients with GC. Methods The PubMed and Web of Science were used for a systematic literature review of GC related to RHOA. The included studies were obtained from two literature databases from past to Aug 31, 2021, by searching keywords. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The odds ratios (ORs) and 95% confidential intervals (CIs) for clinical features were estimated according to the high and low protein expression levels of RhoA. The mean effect sizes of ORs were obtained using the random-effects and fixed-effects models of meta-analysis. Heterogeneity of the studies was assesed by using statistics: τ2, I2; and Q values. The symmetry of funnel plots were inspected for publication bias. Results Finally, 10 studies including 1,389 patients with GC (735 RHOA-positive and 654 RHOA-negative) were eligible for our meta-analysis to estimate associations between the protein expression and clinical features (e.g., Union for International Cancer Control [UICC] stage progression, differentiation, Lauren histological classification, and vascular invasion). In our meta-analysis, RHOA positive expression was determined to have a statistically significant association with UICC stage progression (P = 0.02) and poorly differentiated status (P = 0.02). The association between RHOA positivity and Lauren subtypes was not statistically significant (P = 0.07). Conclusions This meta-analysis suggested that RhoA protein expression in patients with GC was associated with clinical features: UICC stage progression and poorly differentiated status. Our findings are inconclusive but indicate that high RHOA protein expressing patients with GC could predict advanced UICC stages. A large prospective cohort study is required for validation in future.

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“…CLDN18.2, an epithelial tight junction protein, is strictly confined to tight junctions in the gastric mucosa. However, in GC, perturbations in cell polarity lead to CLDN18.2 being exposed on the cancer cell surface and targetable by antibodies [ 28 , 29 ]. AMG 910, an antibody construct designed to engage CD3-positive T cells with CLDN18.2-expressing GC cells, whose anti-tumor effect for CLDN18.2-positive GC or gastroesophageal junction (GEJ) adenocarcinoma is now studied, is expected to be effective [ 30 ].…”

Section: Genomics For Diffuse-type Gastric Cancer and Possible Therap...mentioning

confidence: 99%

Gastric cancer and genomics: review of literature

2022

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Gastric cancer (GC) is a major health concern in many countries. GC is a heterogeneous disease stratified by histopathological differences. However, these variations are not used to determine GC management. Next-generation sequencing (NGS) technologies have become widely used, and cancer genomic analysis has recently revealed the relationships between various malignant tumors and genomic information. In 2014, studies using whole-exome sequencing (WES) and whole-genome sequencing (WGS) for GC revealed the entire structure of GC genomics. Genomics with NGS has been used to identify new therapeutic targets for GC. Moreover, personalized medicine to provide specific therapy for targets based on multiplex gene panel testing of tumor tissues has become of clinical use. Recently, immune checkpoint inhibitors (ICIs) have been used for GC treatment; however, their response rates are limited. To predict the anti-tumor effects of ICIs for GC and to select patients suitable for ICI treatment, genomics also provides informative data not only of tumors but also of tumor microenvironments, such as tumor-infiltrating lymphocytes. In therapeutic strategies for unresectable or recurrent malignant tumors, the target is not only the primary lesion but also metastatic lesions, and metastatic lesions are often resistant to chemotherapy. Unlike colorectal carcinoma, there is a heterogeneous status of genetic variants between the primary and metastatic lesions in GC. Liquid biopsy analysis is also helpful for predicting the genomic status of both primary and metastatic lesions. Genomics has become an indispensable tool for GC treatment and is expected to be further developed in the future.

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Claudins and Gastric Cancer: An Overview

Cited by 69 publications

References 129 publications

Bioinformatics analysis of the prognostic and immunotherapeutic significance of NPRL2 in stomach adenocarcinoma

Bioinformatics analysis of the prognostic and immunotherapeutic significance of NPRL2 in stomach adenocarcinoma

RHOA protein expression correlates with clinical features in gastric cancer: a systematic review and meta-analysis

Gastric cancer and genomics: review of literature

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