晚期胃癌中Claudin 18.2表达的临床病理意义和免疫治疗结果:一项回顾性研究。

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-02-29 DOI:10.21147/j.issn.1000-9604.2024.01.08
Changsong Qi, Xiaoyi Chong, Ting Zhou, Mingyang Ma, Jifang Gong, Miao Zhang, Jian Li, Jun Xiao, Xiaohui Peng, Zhen Liu, Zonghai Li, Lin Shen, Xiaotian Zhang
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引用次数: 0

摘要

目的在不同的临床研究中,克劳丁18同工酶2阳性(CLDN18.2阳性)胃癌(GC)的免疫治疗结果和临床特征各不相同,因此很难优化抗CLDN18.2治疗。我们进行了一项回顾性分析,探讨CLDN18.2表达与GC临床病理特征和免疫治疗结果的关系:分析纳入了2019年至2021年参加CT041-CG4006和CT041-ST-01临床试验的536例晚期GC患者。CLDN18.2表达≥40%的肿瘤细胞(2+,40%)和CLDN18.2表达≥70%的肿瘤细胞(2+,70%)被认为是GC阳性表达的两个水平。根据CLDN18.2的表达情况分析了GC患者的临床病理特征和免疫治疗结果:57.6%(临界值:2+,40%)和48.9%(临界值:2+,70%)的患者表达CLDN18.2。19.8%的患者[合并阳性评分(CPS)≥1,CLDN18.2(截止值:2+,40%)]和17.2%的患者[CPS≥5,CLDN18.2(截止值:2+,70%)]中程序性死亡配体1(PD-L1)和CLDN18.2共同表达。CLDN18.2的表达与年轻、女性、非胃食管交界处(non-GEJ)和弥漫表型呈正相关(P0.05)。子宫附件转移(PConclusions:CLDN18.2阳性GC与预后不良和免疫治疗效果较差有关。抗CLDN18.2疗法、抗PD-L1/PD-1疗法和化疗联合治疗GC需要进一步研究。
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Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer: A retrospective study.

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 anti-CLDN18.2 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-01 clinical 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 (non-GEJ), 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 (irPFS) 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.

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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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