Expression And Significance Of Hypoxia Inducible Factor-2α And Micro RNA-150 In Hepatocellular Carcinoma

Background:In recent years,the death rate of cancer has been increasing year by year.Primary liver cancer(hepatocellular carcinoma,HCC)is one of the six largest cancers in the world,and it is also the third most common cause of cancer death in the world.According to the statistical results in 2014,the incidence of liver cancer in China is about 360000,and the number of deaths is about 31900.The mortality rate ranks second among all malignant tumors,which poses a great threat to human health.The diagnosis of liver cancer mainly depends on imaging examination,but due to the radioactivity of imaging examination,patients can not carry out frequent examination,which reduces the probability of early diagnosis.Liver biopsy is also an accurate diagnostic method,but its related shortcomings,including invasiveness and poor patient compliance,limit its wide application.On the contrary,serum tumor markers are easy to operate and favored by patients and doctors.Screening for early serological markers in patients at high risk of HCC may reduce cancer-related mortality and medical costs.However,there is a lack of early symptoms and biomarkers for early diagnosis in clinic.Most patients usually progress to the late stage from discovery to diagnosis,and do not have the opportunity to receive radical treatment such as liver transplantation,hepatectomy and ablation.Even with surgery,chemotherapy and other treatment measures,there is still a high recurrence rate and mortality.Hypoxia microenvironment is a common feature of most tumors.The tolerance mechanism of cancer cells to long-term hypoxia may lead to abnormal gene transcription or translation.Hypoxia-inducible factor(HIF),as the main transcriptional activator of cell hypoxia perception and adaptation,regulates the expression of many genes at DNA and epigenetic level.Its role can lead to changes in mitochondrial oxidative metabolism,glucose uptake and oxidation,energy production and angiogenesis,resulting in cancer cell proliferation,migration and survival.Therefore,HIF plays an important role in the occurrence and development of tumor.In the process of tumorigenesis and development,micro RNA(mi RNA)can be used not only as an oncogene,but also as a tumor suppressor gene to regulate tumor cell proliferation,apoptosis and differentiation,and play a role in promoting or inhibiting tumor occurrence and development,and more and more evidence shows that abnormal expression of micro RNA has a close relationship with tumor occurrence and development.Therefore,the exploration of HIF and m RNA will help us to find an effective marker to achieve early detection of liver cancer and improve the prognosis of patients.Objective:To investigate the expression and significance of hypoxic inducible factor-2 α and micro RNA-150 in HCC,to investigate the expression of differentially expressed genes in liver cancer and adjacent tissues,and to explore the expression levels of differentially expressed genes in pathological tissues and blood of clinical patients.Method:1.Bioinformatics analysisThe gene expression data of liver cancer were downloaded through TCGA database,ID conversion was carried out through Perl command,survival analysis was carried out through osluca,and then GSEA function enrichment analysis was carried out2.Experimental verification1)Collect liver cancer tissues and adjacent tissues of clinical patients,blood of liver cancer patients and blood of healthy volunteers;2)The tissues of HCC and adjacent tissues were detected by HIF-2α immunohistochemistry and analyzed.3)The expression of HIF-2 α in serum was detected by ELISA and analyzed.4)RNA was extracted from hepatocellular carcinoma and paracancerous tissues,and the expression of hsa-mi R-150-5p was detected by q PCR.5)RNA was extracted from the blood of patients with liver cancer and healthy volunteers,and the expression of hsa-mi R-150-5p was detected by q PCR.Results:1.Bioinformatics analysis showed that there was a significant difference in the expression of HIF-2αand hsa-mi R-150-5p in HCC and paracancerous tissues,P< 0.05,and there was correlation.Survival analysis showed that the prognosis of the group with high expression of HIF-2 α and hsa-mi R-150-5p was better than that of other groups.2.The results of immunohistochemistry showed that the positive cell density of liver cancer tissue samples was significantly lower than that of paracancerous tissues,and the average optical density of liver cancer tissue samples was also significantly lower than that of paracancerous samples.The results showed that the positive rate of HIF-2α in HCC was lower than that in paracancerous tissues.3.The results of ELISA showed that the concentration of HIF-2α in the blood of patients with liver cancer was significantly lower than that of healthy volunteers,P< 0.05.4.The results of real-time fluorescence quantitative PCR detection showed that the expression of hsa-mi R-150-5p in liver cancer tissues was significantly lower than that in adjacent tissues(P< 0.05),and the expression of hsa-mi R-150-5p in blood of patients with liver cancer was significantly lower than that in healthy patients.Conclusion:The occurrence and progression of HCC is associated with HIF-2α and hsa-mir-150-5p,and the high expression of HIF-2α and hsa-mir-150-5p in HCC patients also suggests a good prognosis,HIF-2α and hsa-mi R-150-5p can be used as potential indicators to judge the prognosis of HCC.The mechanism of HIF-2α and hsa-mir-150-5p in hepatocellular carcinoma has not been explored,and further studies are needed.