NDLI: LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway

Content Provider	Springer Nature : BioMed Central
Author	Tan, Yuen Chen, Qingchuan Pan, Siwei An, Wen Xu, Huimian Xing, Yao Zhang, Jianjun
Abstract	Background The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. Methods We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. Results The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. Conclusion LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-09541-0.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-09541-0
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-04-30
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Lauren classification WGCNA LMOD1 FAK-Akt/mTOR Peritoneal metastasis Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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