Metastatic Lymph Node 64 (MLN64) Expression in Gastric Cancer: The Clinical and Molecular Implications in Drug Resistance.

IF 2.6 4区 医学 Q2 GENETICS & HEREDITY Cancer Genomics & Proteomics Pub Date : 2024-01-01 DOI:10.21873/cgp.20427
Amber Xinyu Li, Jimmy Jianyuan Zeng, Elyas Khan, Q Ping Dou, Xinguo Zhuang, Edison Ke Ji, Fiona Ruge, Tracey A Martin, Shuqin Jia, Wen G Jiang
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引用次数: 0

Abstract

Background/aim: Metastatic lymph node 64 (MLN64) is often co-amplified with ERBB2 (HER2) and plays a role in the progression of breast and prostate cancer. The present study explored the expression of MLN64 in clinical gastric cancer in association with the ERBB family and its impact on drug resistance in patients.

Materials and methods: Two independent gastric cancer cohorts (n=324; n=87) were used to explore the expression profile of MLN64 in conjunction with ERBB family members in clinical gastric cancer and its association with neoadjuvant chemotherapy responses. Gastric cancer AGS and HCG27 cells with MLN64 knockdown were generated to determine the function of MLN64 in cell behavioural changes.

Results: Gastric tumor tissues expressed significantly higher levels of MLN64 compared with normal tissues (p<0.01); however, MLN64 alone was a weak prognostic indicator. An integrated co-expression of MLN64, ERBB4, and NRG4 was a significant factor in assessing overall survival in both cohorts. MLN64 was a profound indicator of patient response to neoadjuvant chemotherapy. In vitro studies indicated a significant contribution of MLN64 to the response of gastric cancer cells to chemodrugs and Her-2 inhibitors. MLN64 knockdown also contributed to the adhesion and migration and suggested a possible mechanism mediated by the interaction between MLN64 and ERBBs.

Conclusion: MLN64 is an indicator of patient response to neoadjuvant chemotherapy in gastric cancer. Together with the expression pattern of ERBB4, MLN64 is a poor prognostic factor for patients with gastric cancer.

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胃癌中转移淋巴结 64 (MLN64) 的表达:耐药性的临床和分子影响。
背景/目的:转移淋巴结64(MLN64)通常与ERBB2(HER2)共同扩增,并在乳腺癌和前列腺癌的进展中发挥作用。本研究探讨了MLN64与ERBB家族在临床胃癌中的表达及其对患者耐药性的影响:采用两个独立的胃癌队列(n=324;n=87)探讨MLN64与ERBB家族成员在临床胃癌中的表达谱及其与新辅助化疗反应的关系。为了确定MLN64在细胞行为变化中的功能,还生成了敲除MLN64的胃癌AGS和HCG27细胞:结果:与正常组织相比,胃癌组织表达的 MLN64 水平明显更高(p):MLN64是胃癌患者对新辅助化疗反应的指标。连同ERBB4的表达模式,MLN64是胃癌患者的不良预后因素。
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来源期刊
Cancer Genomics & Proteomics
Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY
CiteScore
5.00
自引率
8.00%
发文量
51
期刊介绍: Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.
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