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E-钙黏蛋白表达降低与胃癌预后不良及临床病理特征不良相关:一项荟萃分析。

Reduced expression of E-cadherin correlates with poor prognosis and unfavorable clinicopathological features in gastric carcinoma: a meta-analysis.

机构信息

Department of General Surgery (Key Disciplines of Medicine in Quzhou City), Longyou County People’s Hospital, Longyou People’s Hospital Affiliated with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Quzhou 324400, China.

Department of General Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China.

出版信息

Aging (Albany NY). 2024 Jun 12;16(12):10271-10298. doi: 10.18632/aging.205929.

Abstract

BACKGROUNDS

Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the development and progression of GC as an adhesive, invasive suppressor gene. Whether reduced E-cadherin has an impact on prognosis, clinicopathological features for GC has been well studied, but no conclusive results has been obtained.

METHODS

Eligible studies and relevant data were obtained from PubMed, Elsevier, Embase, Cochrane Library and Web of Science databases until June 30, 2023. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Correlation of E-cadherin expression with overall survival (OS), clinicopathological features and risk factors were evaluated.

RESULTS

36 studies fulfilled the selected criteria. 9048 cases were included. This meta-analysis showed that patients with GC with reduced E-cadherin had unfavourable clinicopathological features and poor OS. The pooled ORs of one-, three- and five-year OS were 0.38 ( = 25 studies, 95%CI: 0.25-0.57, Z = 4.61, < 0.00001), 0.33 ( = 25 studies, 95% CI: 0.23-0.47, Z = 6.22, < 0.00001), 0.27 ( = 22 studies, 95% CI: 0.18-0.41, Z = 6.23, < 0.00001), respectively. Moreover, reduced E-cadherin expression significantly correlated with differentiation grade (OR = 0.29, 95% CI: 0.22-0.39, Z = 8.58, < 0.00001), depth of invasion (OR = 0.49, 95% CI: 0.36-0.66, Z = 4.58, < 0.00001), lymphatic node metastasis (OR = 0.49, 95% CI: 0.38-0.64, Z = 5.38, < 0.00001), distant metastasis (OR = 2.24, 95% CI: 1.62-3.09, Z = 4.88, < 0.00001), peritoneal metastasis (OR = 2.17, 95% CI: 1.39-3.39, Z = 3.40, = 0.0007), TNM stage (OR = 0.41, 95% CI: 0.28-0.61, Z = 4.44, < 0.00001), lymphatic vessel invasion (OR = 1.77, 95% CI: 1.11-2.82, Z = 2.39, = 0.02), vascular invasion (OR = 1.55, 95% CI: 1.22-1.96, Z = 3.58, = 0.0003), Lauren type (OR = 0.35, 95% CI: 0.21-0.57, Z = 4.14, < 0.0001), Borrmann classification (OR = 0.50, 95% CI: 0.25-0.99, Z = 1.97, = 0.048) and tumor size (≥5 cm vs. <5 cm: OR = 1.73, 95% CI: 1.34-2.23, Z = 4.19, < 0.0001; ≥6 cm vs. <6 cm: OR = 2.29, 95% CI: 1.51-3.49, Z = 3.87, = 0.0001). No significant association was observed between reduced E-cadherin expression and liver metastasis, perineural invasion, alcohol consumption, smoking status, familial history, Helicobacter pylori (HP) infection.

CONCLUSIONS

The reduced expression of E-cadherin is significantly correlated with poor OS and unfavourable clinicopathological features in GC. The expression level of E-cadherin not only serves as a predictor for disease progression and prognosis in GC but also emerges as a novel therapeutic target.

摘要

背景

胃癌(GC)是全球最致命的人类恶性肿瘤之一,中位生存时间不到 1 年。E-钙黏蛋白作为一种黏附性、侵袭抑制基因,在 GC 的发生和发展中发挥着重要作用。E-钙黏蛋白的减少是否对预后、GC 的临床病理特征有影响,已经进行了大量研究,但没有得出明确的结论。

方法

从 PubMed、Elsevier、Embase、Cochrane Library 和 Web of Science 数据库中获取符合条件的研究和相关数据,截至 2023 年 6 月 30 日。使用固定或随机效应模型计算汇总优势比(OR)和 95%置信区间(CI)。评估 E-钙黏蛋白表达与总生存期(OS)、临床病理特征和危险因素的相关性。

结果

符合入选标准的 36 项研究纳入了 9048 例患者。这项荟萃分析表明,E-钙黏蛋白表达减少的 GC 患者具有不良的临床病理特征和较差的 OS。汇总的 1、3 和 5 年 OS 的 OR 分别为 0.38( = 25 项研究,95%CI:0.25-0.57,Z = 4.61, < 0.00001)、0.33( = 25 项研究,95%CI:0.23-0.47,Z = 6.22, < 0.00001)、0.27( = 22 项研究,95%CI:0.18-0.41,Z = 6.23, < 0.00001)。此外,E-钙黏蛋白表达的减少与分化程度(OR = 0.29,95%CI:0.22-0.39,Z = 8.58, < 0.00001)、浸润深度(OR = 0.49,95%CI:0.36-0.66,Z = 4.58, < 0.00001)、淋巴结转移(OR = 0.49,95%CI:0.38-0.64,Z = 5.38, < 0.00001)、远处转移(OR = 2.24,95%CI:1.62-3.09,Z = 4.88, < 0.00001)、腹膜转移(OR = 2.17,95%CI:1.39-3.39,Z = 3.40, = 0.0007)、TNM 分期(OR = 0.41,95%CI:0.28-0.61,Z = 4.44, < 0.00001)、淋巴管侵犯(OR = 1.77,95%CI:1.11-2.82,Z = 2.39, = 0.02)、血管侵犯(OR = 1.55,95%CI:1.22-1.96,Z = 3.58, = 0.0003)、Lauren 分型(OR = 0.35,95%CI:0.21-0.57,Z = 4.14, < 0.0001)、Borrmann 分级(OR = 0.50,95%CI:0.25-0.99,Z = 1.97, = 0.048)和肿瘤大小(≥5 cm 比<5 cm:OR = 1.73,95%CI:1.34-2.23,Z = 4.19, < 0.0001;≥6 cm 比<6 cm:OR = 2.29,95%CI:1.51-3.49,Z = 3.87, = 0.0001)显著相关。E-钙黏蛋白表达的减少与肝转移、神经侵犯、饮酒、吸烟、家族史、幽门螺杆菌(HP)感染无关。

结论

E-钙黏蛋白表达的减少与 GC 的 OS 不良和不良的临床病理特征显著相关。E-钙黏蛋白的表达水平不仅是 GC 疾病进展和预后的预测指标,也是一种新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bc0/11236327/275fe0fe33f2/aging-16-205929-g001.jpg

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