Discovery And Functional Study Of Liver Cancer Metastasis Related Gene NPNT Based On Bioinformatics Analysis

Liver cancer is a common malignant tumor.The incidence and mortality of liver cancer are among the highest in the world,and it is the third leading cause of cancer-related death.According to statistics,there were 905,677 new cases of liver cancer and 830,180 deaths from liver cancer worldwide in2020,mainly distributed in East Asia,Southeast Asia,North Africa and West Africa.Liver cancer is the second leading cause of cancer death in China.In recent decades,studies have shown that the incidence and mortality of liver cancer in the middle and lower reaches of the Yangtze River are significantly higher than those in the central and western regions of China.Due to its high mortality and poor prognosis,liver cancer has become a serious disease burden in China.At present,the treatment of liver cancer is mainly surgery,radiotherapy,chemotherapy,immunotherapy and Traditional Chinese medicine.Although surgical treatment is the most effective treatment,most Hepatocellular Carcinoma(HCC)patients are already in the middle and advanced stage when they are first diagnosed,which is not suitable for surgical treatment.Postoperative resection has a high recurrence rate and liver transplantation failure rate.Radiotherapy and chemotherapy have great toxicity and side effects.Immunotherapy and targeted therapy are important adjuvant therapies,but their clinical application is limited due to the lack of corresponding therapeutic targets,and the treatment of liver cancer still faces great challenges.Tumor metastasis is the main cause of death of HCC.Therefore,it is of great significance for the treatment of liver cancer and the development of new targeted drugs to explore potential targets related to liver cancer metastasis and explore the potential molecular mechanism of liver cancer metastasis.Nephronectin(NPNT)is highly expressed in a variety of cancer tissues and promotes tumor proliferation,migration and invasion,but its mechanism in liver cancer metastasis has not been reported.In this study,we mined gene modules related to liver cancer metastasis through weighted gene co-expression network analysis(WGCNA),and finally identified the key gene NPNT through multiple bioinformatics methods.Subsequently,the mechanism of NPNT in HCC metastasis was preliminarily discussed.The research contents are as follows:(1)Gene modules highly positively correlated with HCC metastasis were screened by WGCNA analysis.(2)Multiple bioinformatics analysis methods(differential gene expression analysis,GO/KEGG analysis,survival analysis,Cox regression analysis,etc.)showed that NPNT was a potential key gene associated with HCC metastasis.High expression of NPNT in HCC was confirmed by expression analysis and immunohistochemistry.(3)The effects of NPNT on the proliferation and invasion of HCC cells were detected by Small interfering Ribonucleic Acid(si RNA)transfection,MTT assay,cell scratch assay and Transwell assay.(4)GSEA(Gene Set Enrichment Analysis)and Western blot assay were used to preliminarily explore the mechanism of NPNT promoting the invasion of HCC cells.Research Conclusions:(1)Compared with paracancer,NPNT was highly expressed in HCC.NPNT was highly expressed in metastatic HCC compared with non-metastatic HCC.(2)Survival analysis and univariate and multivariate Cox analysis showed that NPNT could be an independent risk factor for adverse survival of HCC.(3)Interference of NPNT expression can inhibit the invasion of HCC cells and the FAK/PI3K/AKT signaling pathway.