Identification of CFHR4 associated with poor prognosis of hepatocellular carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is one of the most leading causes of cancer death worldwide. The 5-year survival rate of HCC patients remains low due to the lack of early-stage symptoms. Human complement factor H-related protein 4 (CFHR4) is a critical gene that belongs to the factor H family of plasma glycoproteins, which has not been linked to HCC development. The correlations between CFHR4 and prognosis and tumor-infiltrating lymphocytes in HCC are yet unknown. The present study demonstrated the involvement of CFHR4 in HCC via data mining approaches.ResultsA total of 18 upregulated and 67 down-regulated differentially expressed genes (DEGs) were identified. Importantly, CFHR4, which was screened from DEGs, was shown to express at a lower level in HCC tumor tissue than normal tissues. Western blotting (WB), immunohistochemical (IHC) and quantitative reverse transcription PCR (qRT-PCR) experiments of clinical samples further validated CFHR4 was aberrantly expressed in HCC patients; Data from TCGA showed that CFHR4 was inversely correlated with a cancer family history, histological grade, tumor node metastasis (TNM) stage, and serum AFP level of HCC patients; Univariate and multivariate analyses revealed that low expression of CFHR4 was an independent predictive marker in patients with HCC; Kaplan-Meier analysis showed that the lower expression of CFHR4 was significantly associated with the progression of HCC and poor prognosis rates. Furthermore, TIMER analysis indicated that CFHR4 expression levels had correlations with infiltrating levels of immune cells in HCC.ConclusionCFHR4 expression was low in HCC and was significantly related to the poor prognosis of HCC and the level of immune infiltration. CFHR4 played important roles in regulating the initiation and progression of HCC and could be a potential biomarker for the diagnosis and prognosis of HCC.MethodsThe expression of CFHR4 was analyzed by GEO and TCGA-LIHC database and verified by WB and IHC assay. The biological function of CFHR4 was performed by GO and KEGG enrichment analysis, and the genomic alteration of CFHR4 was investigated by cBioPortal database.The correlation between CFHR4 expression and clinical relevance was evaluated through Cox proportional hazards model, and the correlation between CFHR4 expression and tumor immune infiltrates were studied by TIMER database.

Identification prognostic features related to sphingolipid metabolism and experimental validation of TRIM47 in hepatocellular carcinoma

“…High expression of TRIM47 is associated with poorer overall survival in HCC patients [17]. High G6PD and LPCAT levels suggested a poor prognosis for HCC patients [25][26][27], while CFHR4 was the opposite [28]. This is consistent with our results.…”

CYB5D2 inhibits the malignant progression of hepatocellular carcinoma by inhibiting TGF-β expression and epithelial-mesenchymal transition

“…This analysis highlights their potential role in HCC progression and patient prognostic outcomes. Research by Ding Q et al pointed out that CFHR4 is signi cantly low-expressed in HCC, which can lead to poor patient prognosis, and its level of expression and the extent of immune cell in ltration are also correlated (32). The study by Yu H et al further showed the substantial predictive usefulness of CFHR4 in HCC by demonstrating how the expression of this gene and several clinicopathological factors are strongly correlated with immune cell in ltration (33).…”

Identification of oncogenes and tumor-suppressor genes with hepatocellular carcinoma: A comprehensive analysis based on TCGA and GEO datasets

“…There is an urgent need to find new targets for the diagnosis and treatment of liver cancer in the direction of a breakthrough in the current treatment limitations. Some previous studies used TCGA and GEO databases to screen oncogenes and identify prognostic or immune-related genes ( Chen et al, 2020 ; Gao et al, 2021 ; Yan et al, 2021 ; Shen et al, 2022a ; Shen et al, 2022b ; Ding et al, 2022 ; Gao et al, 2022 ; Long et al, 2022 ; Yang et al, 2022 ). However, in this study, four GSE datasets, GSE36376, GSE102079, GSE54236, and GSE45267, were summarized for analysis, hoping to find the mechanism of cancer-promoting and tumor-suppressor factors in liver cancer from the perspective of improving the accuracy of the research results.…”

“…Currently, public data and bioinformatic analysis methods have provided us with invaluable resources to find HCC-related oncogenes and tumor-suppressor genes. Some studies searched cancer-related target genes through public databases, whether prognostic oncogene identification ( Gao et al, 2021 ; Yan et al, 2021 ; Shen et al, 2022a ; Gao et al, 2022 ), single-gene research studies ( Ding et al, 2022 ; Yang et al, 2022 ), or immune-related oncogenes ( Chen et al, 2020 ; Shen et al, 2022b ; Long et al, 2022 ), all of which provided a strong basis for targeted therapy and precise treatment of liver cancer. However, many studies only consider the differential expression of oncogenes in tumors, ignoring the important role and potential association of tumor-suppressor genes.…”