膜联蛋白 A10 在胃癌细胞中的转录组分析及其与化疗敏感性的关系

Transcriptomic Analysis of Annexin A10 and Chemosensitivity in Gastric Adenocarcinoma Cells.

机构信息

Institute for Clinical Laboratory, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.

Institute for Clinical Laboratory, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan;

出版信息

Anticancer Res. 2022 Apr;42(4):1707-1717. doi: 10.21873/anticanres.15647.

DOI:10.21873/anticanres.15647

PMID:35346989

Abstract

BACKGROUND/AIM: Gastric cancer (GC) is the third-leading cause of cancer-related deaths worldwide; thus, novel diagnostic and therapeutic biomarkers are needed. Annexin A10 (ANXA10) is a calcium- and phospholipid-binding protein. As far as we are aware, there are no reports describing the detailed functions of ANXA10 in GC. Therefore, we investigated the downstream mRNA variation and the effects of ANXA10 on chemoresistance in GC cell lines.

MATERIALS AND METHODS

ANXA10 knockout GC cell lines were generated, and we performed functional analyses, chemosensitivity drug testing, and microarray analyses. Additionally, immunohistochemistry for ANXA10 was performed on 40 patients with GC who had received 5-fluorouracil (5-FU)-based chemotherapy to compare their prognosis and clinicopathological factors.

RESULTS

ANXA10 knockout GC cells showed significantly increased proliferation, invasion, and sensitivity to 5-FU. The overall survival of ANXA10-positive cases was considerably lower than that of ANXA10-negative cases in GC patients who received 5-FU-based chemotherapy. Microarray analysis revealed candidate pathways regulated by ANXA10 and claudin 1 (CLDN1), keratin 80 (KRT80), RANBP2-type and C3HC4-type zinc finger containing 1 (RBCK1), and solute carrier family 7 member 5 (SLC7A5) genes.

CONCLUSION

ANXA10 knockout increased the susceptibility of GC cell lines to 5-FU; ANXA10 may be a predictive indicator for response to 5-FU treatment in GC cases. ANXA10 may be involved in the pathogenesis of GC, in collaboration with CLDN1, KRT80, RBCK1, and SLC7A5.

摘要

背景/目的：胃癌（GC）是全球导致癌症相关死亡的第三大原因；因此，需要新的诊断和治疗生物标志物。膜联蛋白 A10（ANXA10）是一种钙和磷脂结合蛋白。据我们所知，尚无报道描述 ANXA10 在 GC 中的详细功能。因此，我们研究了 GC 细胞系中 ANXA10 的下游 mRNA 变化及其对化疗耐药性的影响。

材料和方法

生成了 ANXA10 敲除 GC 细胞系，并进行了功能分析、化疗药物敏感性测试和微阵列分析。此外，对 40 例接受基于 5-氟尿嘧啶（5-FU）的化疗的 GC 患者进行了 ANXA10 的免疫组织化学分析，以比较其预后和临床病理因素。

结果

ANXA10 敲除 GC 细胞表现出明显增加的增殖、侵袭和对 5-FU 的敏感性。接受基于 5-FU 的化疗的 GC 患者中，ANXA10 阳性病例的总生存率明显低于 ANXA10 阴性病例。微阵列分析显示了由 ANXA10 和紧密连接蛋白 1（CLDN1）、角蛋白 80（KRT80）、RANBP2 型和 C3HC4 型锌指含 1（RBCK1）以及溶质载体家族 7 成员 5（SLC7A5）基因调节的候选途径。