Pharmacogenomics and Personalized Medicine (Nov 2021)
Prognostic Value of LHFPL Tetraspan Subfamily Member 6 (LHFPL6) in Gastric Cancer: A Study Based on Bioinformatics Analysis and Experimental Validation
Abstract
Yuan-Jie Liu,1– 3,* Sheng-Yan Yin,2,3,* Shu-Hong Zeng,2,3 Yi-Dou Hu,1 Meng-Qi Wang,2,3 Pan Huang,1 Jie-Pin Li1– 3 1Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 2Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 3No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie-Pin Li; Pan HuangDepartment of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Chang ‘an South Road No. 77, Zhangjiagang, Jiangsu, 215600, People’s Republic of ChinaTel +8615150224526; +8613921976647Email [email protected]; [email protected]: The identification of biomarkers and effective therapeutic targets for gastric cancer (GC), the most common cause of cancer-related deaths around the world, is currently a major focus in research. Here, we examined the utility of LHFPL6 as a prognostic biomarker and therapeutic target for GC.Methods: We explored the clinical relevance, function, and molecular role of LHFPL6 in GC using the MethSurv, cBioPortal, TIMER, Gene Expression Profiling Interactive Analysis, ONCOMINE, MEXPRESS, and EWAS Atlas databases. The GSE118919, GSE29272, and GSE13861 datasets were used for differential expression analysis. Using The Cancer Genome Atlas, we developed a Cox regression model and assessed the clinical significance of LHFPLs. In addition, we used the “CIBERSORT” algorithm to make reliable immune infiltration estimations. Western blot and immunohistochemistry were used to examine protein expression. Cell migration and invasion were assessed using transwell experiments. THP-1-derived macrophages and GC cells were co-cultured in order to model tumor–macrophage interactions in vitro. The levels of CD206 and CD163 were measured using immunofluorescence assays. The results were visualized with the “ggplot2” and “circlize” packages.Results: Our results showed that in GC, LHFPL6 overexpression was significantly associated with a poor prognosis. Our findings also suggested that LHFPL6 may be involved in the activation of the epithelial–mesenchymal transition. Furthermore, LHFPL6 expression showed a positive correlation with the abundance of M2 macrophages, which are potent immunosuppressors.Conclusion: LHFPL6 could be a prognostic biomarker and therapeutic target for GC.Keywords: gastric cancer, LHFPL6, biomarker, EMT, M2 macrophages
