Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18....Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.展开更多
目的探讨Survivin、胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA-binding protein 3,IMP3)及Claudin1在浆膜腔积液细胞蜡块中的表达及临床意义。方法收集我院病理科2017年2月~2021年11月行免疫组化检查且临床资...目的探讨Survivin、胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA-binding protein 3,IMP3)及Claudin1在浆膜腔积液细胞蜡块中的表达及临床意义。方法收集我院病理科2017年2月~2021年11月行免疫组化检查且临床资料齐全的浆膜腔积液细胞块95例,其中恶性84例,良性11例(对照组)。应用免疫组化方法检测浆膜腔积液细胞蜡块中Survivin、IMP3及Claudin1蛋白的表达情况,并对比分析其在良恶性浆膜腔积液以及不同恶性肿瘤中的差异。结果恶性胸膜腔积液病例中胸腔积液53例,腹腔积液31例。肺腺癌41例,消化系统腺癌25例,卵巢恶性肿瘤9例,其他恶性肿瘤9例。与对照组相比,肺腺癌组及消化系统腺癌组IMP3的表达差异具有统计学意义(P<0.05),消化系统腺癌组Claudin1的表达差异具有统计学意义(P<0.05),其他组别Survivin、IMP3及Claudin1的表达与对照组相比差异均无统计学意义(P>0.05)。结论IMP3及Claudin1在恶性浆膜腔积液判断是否为消化系统腺癌来源时具有鉴别意义,IMP3在肺腺癌来源具有鉴别意义。展开更多
BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer cells.The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researc...BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer cells.The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma.AIM To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma.METHODS This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma.We investigated the effect of CLDN18.2 expression on clinicopathological characteristics(age,sex,histological grade,Lauren classification,family history,metastatic site,HER2 expression)and prognosis for patients with metastatic gastric adenocarcinoma.RESULTS CLDN18.2 expression was positive in 73.8%(48)of the patients.During the median 17.7-mo follow-up period,89.2%(58)of the patients died.Median progression-free survival and overall survival(OS)were 6 mo(95%confidence interval:1.6-10.4)and 12 mo(95%confidence interval:7.5-16.5).There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients.In univariate and multivariate Cox regression analysis,there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS.CONCLUSION CLDN18.2 expression was quite high in patients with gastric adenocarcinoma,identifying the proportion of the patients in whom zolbetuximab would be efficacious.There is no statistically significant correlation with clinicopathological characteristics and OS.CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma,although it is predictive.展开更多
基金supported by Beijing Natural Science Foundation (No. Z20J00105)the National Natural Science Foundation of China (No. 82272627)。
文摘Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.
文摘目的探讨Survivin、胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA-binding protein 3,IMP3)及Claudin1在浆膜腔积液细胞蜡块中的表达及临床意义。方法收集我院病理科2017年2月~2021年11月行免疫组化检查且临床资料齐全的浆膜腔积液细胞块95例,其中恶性84例,良性11例(对照组)。应用免疫组化方法检测浆膜腔积液细胞蜡块中Survivin、IMP3及Claudin1蛋白的表达情况,并对比分析其在良恶性浆膜腔积液以及不同恶性肿瘤中的差异。结果恶性胸膜腔积液病例中胸腔积液53例,腹腔积液31例。肺腺癌41例,消化系统腺癌25例,卵巢恶性肿瘤9例,其他恶性肿瘤9例。与对照组相比,肺腺癌组及消化系统腺癌组IMP3的表达差异具有统计学意义(P<0.05),消化系统腺癌组Claudin1的表达差异具有统计学意义(P<0.05),其他组别Survivin、IMP3及Claudin1的表达与对照组相比差异均无统计学意义(P>0.05)。结论IMP3及Claudin1在恶性浆膜腔积液判断是否为消化系统腺癌来源时具有鉴别意义,IMP3在肺腺癌来源具有鉴别意义。
文摘BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer cells.The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma.AIM To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma.METHODS This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma.We investigated the effect of CLDN18.2 expression on clinicopathological characteristics(age,sex,histological grade,Lauren classification,family history,metastatic site,HER2 expression)and prognosis for patients with metastatic gastric adenocarcinoma.RESULTS CLDN18.2 expression was positive in 73.8%(48)of the patients.During the median 17.7-mo follow-up period,89.2%(58)of the patients died.Median progression-free survival and overall survival(OS)were 6 mo(95%confidence interval:1.6-10.4)and 12 mo(95%confidence interval:7.5-16.5).There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients.In univariate and multivariate Cox regression analysis,there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS.CONCLUSION CLDN18.2 expression was quite high in patients with gastric adenocarcinoma,identifying the proportion of the patients in whom zolbetuximab would be efficacious.There is no statistically significant correlation with clinicopathological characteristics and OS.CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma,although it is predictive.
