Metastatic Lymph Node 64 (MLN64) expression in gastric cancer, the clinical and molecular implications in drug resistance

Li, Amber Xinyu, Zeng, Jimmy Jianyuan, Khan, Elyas, Dou, Q. Ping, Zhuang, Xinguo, Ji, Edison Ke, Ruge, Fiona, Martin, Tracey A. ORCID: https://orcid.org/0000-0003-2690-4908, Jia, Shuqin and Jiang, Wen G. ORCID: https://orcid.org/0000-0002-3283-1111 2024. Metastatic Lymph Node 64 (MLN64) expression in gastric cancer, the clinical and molecular implications in drug resistance. Cancer Genomics & Proteomics 21 (1) , pp. 30-40. 10.21873/cgp.20427

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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 cancers. 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 con-junction with ERBB family members in clinical gastric cancer and its association with neoad-juvant chemotherapy responses. Gastric cancer AGS and HCG27 cells with MLN64 knock-down were generated to determine the function of MLN64 in cell behavioral changes. Results: Gastric tumor tissues expressed significantly increased 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 adhesiveness and migration and suggested a possible mechanism mediated by the in-teraction between MLN64 and ERBBs. Conclusion: MLN64 is an indicator for patient response to neoadjuvant chemotherapies in gastric cancer. Together with the expression pattern of ERBB4, it makes is a poor prognostic factor in gastric cancer patients.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	International Institute of Anticancer Research
ISSN:	1109-6535
Funders:	Cardiff University China Medical Scholarship
Date of First Compliant Deposit:	21 November 2023
Date of Acceptance:	11 October 2023
Last Modified:	24 Jan 2024 13:55
URI:	https://orca.cardiff.ac.uk/id/eprint/164092

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