Functional loss of ARID1A is tightly associated with high PD‐L1 expression in gastric cancer

Kim, Young‐Bae; Ahn, Ji Mi; Bae, Won Jung; Sung, Chang Ohk; Lee, Dakeun

doi:10.1002/ijc.32140

Cited by 83 publications

(76 citation statements)

References 34 publications

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“…3c). These results also support a distinct feature of the INT subtype regarding the response to ICI treatment according to significant enrichment of MSI or EBV along with PIK3CA and ARID1A mutations [5,[14][15][16][17].…”

Section: Mutational Profiling Reveals An Association Between the Cod supporting

confidence: 73%

“…3d). When the expression levels of immune checkpoint genes were compared, CD274 (PD-L1) showed a significant difference in expression between the INT and COD subtypes, supporting a reported close relationship between ARID1A and PD-L1 expression in GC [15][16][17]. Since activation of DNA damage response and repair (DDR) genes is significantly associated with the response to ICI [20], we also estimated the expression levels of DDR genes, revealing that the vast majority of DDR genes were significantly activated in the INT subtype.…”

Section: Mutational Profiling Reveals An Association Between the Cod supporting

confidence: 56%

“…Comparison of CDH1 mutations, which are well-known variants in diffusetype GC, between the INT and COD subtypes revealed that the mutation frequency in the COD group was higher than that in the INT group; however, the difference was not statistically significant. We also observed significantly more mutations of PIK3CA [frequently found in microsatellite unstable (MSI) GCs] [14] and ARID1A (associated with MSI along with hypermutations and PD-L1 expression in cancers including GC) [15][16][17] in the INT subtype compared to the COD subtype. These results suggest distinct features of the INT subtype, including high TMB and MSI, which are typical indicators predicting the response to ICI treatment [5,18,19].…”

Section: Mutational Profiling Reveals An Association Between the Cod mentioning

confidence: 67%

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Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

Kim

Park

et al. 2019

Gastric Cancer

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Background Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for diffuse-type GC have been identified. Here, we aim to identify a prognostic and predictive signature of diffuse-type GC heterogeneity. Methods We analyzed RNA-seq-based transcriptome data to identify a molecular signature in 150 gastric tissue samples including 107 diffuse-type GCs. The predictive value of the signature was verified using other diffuse-type GC samples in three independent cohorts (n = 466). Log-rank and Cox regression analyses were used to estimate the association between the signature and prognosis. The signature was also characterized by somatic variant analyses and tissue microarray analysis between diffuse-type GC subtypes. Results Transcriptomic profiling of RNA-seq data identified a signature which revealed distinct subtypes of diffuse-type GC: the intestinal-like (INT) and core diffuse-type (COD) subtypes. The signature showed high predictability and independent clinical utility in diffuse-type GC prognosis in other patient cohorts (HR 2.058, 95% CI 1.53-2.77, P = 1.76 × 10-6). Integrative mutational and gene expression analyses demonstrated that the COD subtype was responsive to chemotherapy, whereas the INT subtype was responsive to immunotherapy with an immune checkpoint inhibitor (ICI). Tissue microarray analysis showed the practical utility of IGF1 and NXPE2 for predicting diffuse-type GC heterogeneity. Conclusions We present a molecular signature that can identify diffuse-type GC patients who display different clinical behaviors as well as responses to chemotherapy or ICI treatment.

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Section: Mutational Profiling Reveals An Association Between the Cod supporting

confidence: 73%

Section: Mutational Profiling Reveals An Association Between the Cod supporting

confidence: 56%

Section: Mutational Profiling Reveals An Association Between the Cod mentioning

confidence: 67%

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Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

Kim

Park

et al. 2019

Gastric Cancer

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“…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 , …”

Section: Discussionmentioning

confidence: 99%

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

2020

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Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein–Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088–0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096–0.194), 0.103 (95% CI: 0.077–0.137), 0.080 (95% CI: 0.061–0.106), and 0.042 (95% CI: 0.016–0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428–0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.

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“…According to the dyeing intensity: 0, no staining; 1+, weak; 2+, medium intensity; 3+, strong. Then, H-score was calculated according to the following formula: [1 × (% cells 1 +) + 2 × (% cells 2 +) + 3 × (% cells 3 +)] (Kim et al, 2019).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Pharmacologic Blockade of 15-PGDH Protects Against Acute Renal Injury Induced by LPS in Mice

Miao

Liu

et al. 2020

Front. Physiol.

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Prostaglandin pathway plays multiple roles in various physiological and pathological conditions. The present study aimed to investigate the effect of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in the degradation of prostaglandins, on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice. In this study, male C57BL/6J mice were injected intraperitoneally with LPS (10 mg/kg). SW033291, a potent small-molecule inhibitor of 15-PGDH, was used to investigate the therapeutic potential of 15-PGDH inhibition on LPS-induced AKI. We discovered that the expression of 15-PGDH protein was upregulated in kidneys of LPS-stimulated mice, and it was mainly localized in the cytoplasm of renal tubular epithelial cells in renal cortex and outer medulla. SW033291 administration improved the survival rates of mice and attenuated renal injury of mice that were challenged by LPS. Additionally, inhibition of 15-PGDH also reversed LPS-induced apoptosis of renal cells, increased expression of anti-apoptotic protein Bcl-2, and downregulated expression of Fas, caspase-3, and caspase-8. Pretreatment of SW033291 enhanced autophagy in kidney cells after LPS stimulation. Our data also showed that inhibition of 15-PGDH relieved the level of lipid peroxidation and downregulated NADPH oxidase subunits induced by LPS in mice kidneys but had no significant effect on the release of inflammatory factors, such as IL-6, IL-1β, TNF-α, and MCP-1. Our study demonstrated that inhibition of 15-PGDH could alleviate LPS-induced AKI by regulating the apoptosis, autophagy, and oxidative stress rather than inflammation in mice.

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Functional loss of ARID1A is tightly associated with high PD‐L1 expression in gastric cancer

Cited by 83 publications

References 34 publications

Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

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

Pharmacologic Blockade of 15-PGDH Protects Against Acute Renal Injury Induced by LPS in Mice

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