Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma

Abstract

Background: Hepatitis B virus infection had been identified its relationship with liver diseases, including liver tumors. We aimed to explore diagnostic and prognostic values between the Human Leukocyte Antigen (HLA) complex and hepatocellular carcinoma (HCC).Methods: We used the GSE14520 dataset to explore diagnostic and prognostic significance between HLA complex and HCC. A nomogram was constructed to predict survival probability of HCC prognosis. Gene set enrichment analysis was explored using gene ontologies and metabolic pathways. Validation of prognostic values of the HLA complex was performed in the Kaplan-Meier Plotter website.Results: We found that HLA-C showed the diagnostic value (P <0.0001, area under curve: 0.784, sensitivity: 93.14%, specificity: 62.26%). In addition, HLA-DQA1 and HLA-F showed prognostic values for overall survival, and HLA-A, HLA-C, HLA-DPA1 and HLA-DQA1 showed prognostic values for recurrence-free survival (all P ≤ 0.05, elevated 0.927, 0.992, 1.023, 0.918, 0.937 multiples compared to non-tumor tissues, respectively). Gene set enrichment analysis found that they were involved in antigen processing and toll like receptor signalling pathway, etc. The nomogram was evaluated for survival probability of HCC prognosis. Validation analysis indicated that HLA-C, HLA-DPA1, HLA-E, HLA-F and HLA-G were associated with HCC prognosis of overall survival (all P ≤ 0.05, elevated 0.988 and 0.997 multiples compared to non-tumor tissues, respectively).Conclusion: HLA-C might be a diagnostic and prognostic biomarker for HCC. HLA-DPA1 and HLA-F might be prognostic biomarkers for HCC.

Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence

“…Consistent with our findings, HLA-DMB expression in ovarian cancer epithelial cells was associated with CD8 T cell infiltration and a marked improvement in disease survival [27]. Similarly, a recent study showed decreased expression of HLA-DMA, HLA-DMB and HLA-DOA in HBV associated HCC patients [26]. In a recent study, HLA-DRB6 was found to be upregulated among cervical cancer tissues and cell line data [28].…”

“…According to the statistical analysis results, several HLA genes (including HLA-A, HLA-C, HLA-E, HLA-F, HLA-G, HLA-L, HLA-DMB, HLA-DQA2 and HLA-DRA) showed association with different clinicopathological features in both HCC cohorts. Recent studies demonstrated the linkage of all MHC classes with HCC prognosis [26]. Interestingly, according to our results, HLA-E, HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 showed association with improved disease-free survival in both cohorts, emphasizing the need to investigate the functional implications of HLA expression in HCC using pre-clinical and clinical studies.…”

“…In a recent study, HLA-DRB6 was found to be upregulated among cervical cancer tissues and cell line data [28]. Additionally, a decreased expression of HLA-DRB6 was also reported in HCC patients compared to non-tumor liver tissues [26,29]. Furthermore, a cell line based study suggested that the upregulation of HLA-E represents a mechanism of tumor escape from NK cytotoxicity in ovarian cancer and melanoma [30].…”

Construction of Prognostic Risk Model for Small Cell Lung Cancer Based on Immune-Related Genes

“…To take an example, HLA-DPA1and HLA-DPB1, dysregulated in our low-risk group, have been manifested to be associated with the maintenance of long-term immune efficacy after HBV vaccination [ 35 ]. In the field of cancer, HLA-DPA1 activates chemokines and toll-like receptor signaling pathways to regulate hepatocellular carcinoma progression [ 36 ]. HLA-DPB1 can be an antitumor factor to recruit NK cells, CD8 + T cells, and tumor-infiltrating lymphocytes such as Th1 and Tfh into breast cancer [ 37 ].…”

Microphysiological vascularized solid tumor model for drugs and cell therapies screening

“…7G-I). Relative to the tumor regions, ECM regions overexpressed genes involved in ECM protein production (COL1A1, COL1A2, COL6A3, COL3A1, SERPINH1), associated with HCC (THBS1, ANXA1, APP, CD44, LTBP1, HSPB1) [38, [41][42][43][44][45][46], HBV-associated HCC (HLA-E, HLA-C, THY1) [47][48][49][50][51][52][53], and vasculature formation (THBS1, ENG, CDH5, ROBO4) [54] (Fig. 7G).…”