Investigation of Potential Molecular Biomarkers for Diagnosis and Prognosis of AFP-Negative HCC

Abstract

Background Alpha-fetoprotein (AFP) is the most important diagnostic and prognostic index of hepatocellular carcinoma (HCC). AFP-positive HCC can be easily diagnosed based on the serum AFP level and typical imaging features, but a number of HCC patients are negative (AFP < 20 ng/mL) for AFP. Therefore, it is necessary to develop novel diagnostic and prognostic biomarkers for AFP-negative HCC. Methods RNA data from TCGA and differential expression of lncRNAs, miRNAs, and mRNAs were downloaded to analyze the differential RNA expression patterns between AFP-negative HCC tissues and normal tissues. A lncRNA-miRNA-mRNA ceRNA regulatory network was constructed to elucidate the interaction mechanism of RNAs. Functional enrichment analysis of these DEmRNAs was performed to indirectly reveal the mechanism of action of lncRNAs. A PPI network was built using STRING, and the hub genes were identified with Cytoscape. The diagnostic value of hub genes was assessed with receiver operating characteristic (ROC) analysis. And the prognostic value of RNAs in the ceRNA was estimated with Kaplan–Meier curve analysis. Results A total of 131 lncRNAs, 185 miRNA, and 1309 mRNAs were found to be differentially expressed in AFP-negative HCC. A ceRNA network consisting of 12 lncRNA, 23 miRNA, and 74 mRNA was constructed. The top ten hub genes including EZH2, CCNB1, E2F1, PBK, CHAF1A, ESR1, RRM2, CCNE1, MCM4, and ATAD2 showed good diagnostic power under the ROC curve; and 2 lncRNAs (LINC00261, LINC00482), 3 miRNAs (hsa-miR-93, hsa-miR-221, hsa-miR-222), and 2 mRNAs (EGR2, LPCAT1) were found to be associated with the overall survival of AFP-negative patients. Conclusion This study could provide a novel insight into the molecular pathogenesis of AFP-negative HCC and reveal some candidate diagnostic and prognostic biomarkers for AFP-negative HCC.

Insights into the Association Between QSER1 and M2 Macrophages and Remarkable Malignancy Characteristics in Hepatocellular Carcinoma

“… 25–27 However, there are few studies on the prognostic indicators of AFP-negative HCC. 27 In the present study, QSER1 expression levels were found to be strongly correlated with serum AFP levels and postoperative outcome of HCC. This suggests that QSER1 may also be a valid predictive target for outcome in AFP-negative HCC patients.…”

E2F1 as a potential prognostic and therapeutic biomarker by affecting tumor development and immune microenvironment in hepatocellular carcinoma

“…The reasons for choosing E2F1 as the research objective are as follows: E2F1 as one of hub genes in LIHC was demonstrated by this study and was verified by several other studies (48,49). Moreover, the roles of E2F1 in tumorigenesis were investigated in other cancers.…”

High expression of PDZ-binding kinase is correlated with poor prognosis and immune infiltrates in hepatocellular carcinoma

“…The receiver operator characteristic (ROC) curve and AUC estimates can determine the expression of PBK to diagnose the value of HCC. The ROC curves based on the TCGA database in AFP-negative HCC patients showed the AUC of PBK was 0.929 [ 34 ]. In the current study, the ROC curves analysis based on the GEO database shows that the AUC of PBK in GSE84402, GSE76427, GSE62232, and GSE121248 was 0.9541, 0.8799, 0.9975, and 0.9224, respectively.…”