Highly expressed Claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC)
| Autor: | Nandie Wu, Bo Xu, Xiangshan Fan, Fangcen Liu, Xinyun Xu, Baorui Liu, Lin Li, Qin Liu, Jia Wei, Tao Shi, Zhongda Wang, Lixia Yu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty ARID1A medicine.medical_treatment Gastroenterology CDH1 03 medical and health sciences 0302 clinical medicine Internal medicine Signet ring cell carcinoma medicine Copy-number variation biology business.industry Cancer Immunotherapy medicine.disease Exact test 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Immunohistochemistry Original Article business |
| Zdroj: | J Gastrointest Oncol |
| ISSN: | 2078-6891 |
| Popis: | BACKGROUND: Advanced gastric signet-ring cell carcinoma (SRCC) is a specific type of malignant gastric cancer (GC) with distinct poorer survival. Claudin18.2 (CLDN18.2) is a promising neo-biomarker for the treatment of GC. Clinical trials of CLDN18.2-targeted antibody and T cell-based immunotherapy providing promising prospects for the treatment of GC. The effect of antibody therapy depended on the expression rate of CLDN18.2 has been found in clinical trials. This study aimed to determine the prevalence and the therapeutic value of CLDN18.2 in advanced gastric SRCC. METHODS: Expression of CLDN18.2 in 105 formalin-fixed, paraffin-embedded (FFPE) tumor tissues was detected by immunohistochemistry (IHC) and evaluated according to FAST criteria. Next-generation sequencing (NGS) using 416 pan-cancer genes panel was performed to characterize the genomic landscape in 61 advanced gastric SRCC patients. Fisher’s exact test was used to determine gene differences in different CLDN18.2 expression levels. RESULTS: A total number of 105 advanced gastric SRCC samples were analyzed, of which 95.2% (100/105) were positive stained. Moderate-to-strong CLDN18.2 expression was observed in 64.8% (68/105) of all samples. In particularly, 21.0% (22/105) samples had positive staining in more than 90% tumor cells. No significance was found between CLDN18.2 expression and overall survival (OS). NGS results showed that single nucleotide variations (SNVs) could be frequently found in TP53 (26.2%), CDH1 (19.7%), MED12 (18.0%), PKHD1 (18.0%) and ARID1A (11.5%), besides, copy number variations (CNVs) were rich in NOTCH1 (18.0%) and FLT4 (9.8%) in SRCC samples. Moreover, SNVs in GRIN2A was found in 20% of the patients who had CLDN18.2 staining in |
| Databáze: | OpenAIRE |
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