Abstract
BackgroundLiver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death. The purpose of this work is to find new diagnostic biomarkers or prognostic biomarkers and explore the biological functions related to the prognosis of liver cancer.MethodsGSE25097 datasets were firstly obtained and compared with TCGA LICA datasets and an analysis of the overlapping differentially expressed genes (DEGs) was conducted. Cytoscape was used to screen out the Hub Genes among the DEGs. ROC curve analysis was used to screen the Hub Genes to determine the genes that could be used as diagnostic biomarkers. Kaplan-Meier analysis and Cox proportional hazards model screened genes associated with prognosis biomarkers, and further Gene Set Enrichment Analysis was performed on the prognosis genes to explore the mechanism affecting the survival and prognosis of liver cancer patients.Results790 DEGs and 2162 DEGs were obtained respectively from the GSE25097 and TCGA LIHC data sets, and 102 Common DEGs were identified by overlapping the two DEGs. Further screening identified 22 Hub Genes from 102 Common DEGs. ROC and survival curves were used to analyze these 22 Hub Genes and it was found that there were 16 genes with a value of AUC > 90%. Among these, the expression levels of ESR1,SPP1 and FOSB genes were closely related to the survival time of liver cancer patients. Three common pathways of ESR1, FOBS and SPP1 genes were identified along with seven common pathways of ESR1 and SPP1 genes and four common pathways of ESR1 and FOSB genes.ConclusionsSPP1, AURKA, NUSAP1, TOP2A, UBE2C, AFP, GMNN, PTTG1, RRM2, SPARCL1, CXCL12, FOS, DCN, SOCS3, FOSB and PCK1 can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can also be used as prognostic biomarkers. Activation of the cell cycle-related pathway, pancreas beta cells pathway, and the estrogen signaling pathway, while on the other hand inhibition of the hallmark heme metabolism pathway, hallmark coagulation pathway, and the fat metabolism pathway may promote prognosis in liver cancer patients.
Highlights
Liver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death
SPP1, AURKA, NUSAP1, TOP2A, UBE2C, AFP, GMNN, PTTG1, RRM2, SPARCL1, CXCL12, FOS, DCN, SOCS3, FOSB and PCK1 can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can be used as prognostic biomarkers
The risk factors of liver cancer formation are different in 53 countries and throughout different regions in the world
Summary
Liver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death. According to the Global Cancer Statistics report of 2018, liver Cancer became the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death in the world in 2018 [1]. The main risk factors for liver cancer are chronic hepatitis B virus (HBV) [2,3,4], hepatitis C virus (HCV) [5,6,7], aflatoxin-contaminated food [8], heavy alcohol consumption [6, 9, 10], obesity [11], smoking [12] and type 2 diabetes [13, 14]. In most high-risk areas such as China and East Africa, chronic HBV infection and aflatoxin exposure are the main determinants of liver cancer. For low-risk liver cancer areas, an increase in obesity rates is the leading cause of the increase in liver cancer case
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