Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 19:13:913398.
doi: 10.3389/fgene.2022.913398. eCollection 2022.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of Ficolin Family Members in Hepatocellular Carcinoma

Liang Sun  1 , Shian Yu  1 , Cairong Dong  1 , Zhengyi Wu  1 , He Huang  1 , Zhendong Chen  1 , Zhipeng Wu  1 , Xiangbao Yin  1
Affiliations

Comprehensive Analysis of Prognostic Value and Immune Infiltration of Ficolin Family Members in Hepatocellular Carcinoma

Liang Sun et al. Front Genet. .

Abstract

Objective: Ficolin (FCN) family proteins are part of the innate immune system, play a role as recognition molecules in the complement system, and are associated with tumor development. The mechanism of its role in immunotherapy of hepatocellular carcinoma (HCC) is unclear. Methods: In this study, we used the TCGA database, HPA database, Gene Expression Profile Interaction Analysis (GEPIA), Kaplan-Meier plotter, TCGAportal, cBioPortal, GeneMANIA, TIMER, and TISIDB to analyze Ficolin family proteins (FCN1, FCN2 and FCN3, FCNs) in patients with hepatocellular carcinoma for differential expression, prognostic value, genetic alterations, functional enrichment, and immune factor correlation analysis. Results: The expression levels of FCN1/2/3 were significantly reduced in patients with HCC. Among them, FCN3 showed significant correlation with Overall Survival (OS), Progressive Free Survival (PFS) and Relapse Free Survival (RFS) in HCC. FCN1 and FCN3 may be potential prognostic markers for survival in patients with HCC. In addition, the functions of differentially expressed FCNs were mainly related to complement activation, immune response, apoptotic cell clearance and phagocytosis. FCNs were found to be significantly correlated with multiple immune cells and immune factors. Expression of FCN1 and FCN3 differed significantly in the immune and stromal cell component scores of HCC. analysis of the tumor mutation burden (TMB) and microsatellite instability (MSI) of FCNs with pan-cancer showed that FCN3 was significantly correlated with both. Conclusions: Our study provides new insights into the link between the FCN family and immunotherapy for HCC, and FCN3 may serve as a prognostic biomarker for HCC.

Keywords: bioinformatics analysis; ficolin family; hepatocellular carcinoma; immunotherapy; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The expression levels of FCNs in different tumor (TIMER). (A) FCN1; (B) FCN2; (C) FCN3.
FIGURE 2
FIGURE 2
Immunohistochemistry of FCNs in three pairs of HCC tissues. (A) FCN1; (B) FCN2; (C) FCN3.
FIGURE 3
FIGURE 3
The expressions of FCNswere down-regulated in LIHC cells and tissues. (A–C). The mRNA expression of FCNsin 7,702, LM3, 97H, hu7, and 7,721 cell. (D–F). mRNA expression of FCNs in LIHC tissues. *p < 0.05.
FIGURE 4
FIGURE 4
The diagnostic value of FCNs in LIHC patients. (A) FCN1; (B) FCN2; (C) FCN3.
FIGURE 5
FIGURE 5
The diagnostic and prognostic value of FCNs in LIHC. (A) Kaplan-Meier plotter reveals the overall survival (OS) progression free survival (PFS) and relaps-free survival (RFS) curvesbased on the mRNA levels of FCNs in LIHC patients. (B) Overall survival (OS) curves of FCNs in LIHC patients determind using GEPIA. (C) Overall survival (OS) curves of FCNs in LIHC patients determind using TCGAportal.
FIGURE 6
FIGURE 6
FCNs gene mutation and PPI network constraction. (A) Summary of alterations in different expressed FCNs in LIHC. FCNs were altered 21 samples of 853 patients with LIHC, accounting for 2%. (B,C) Protein-protein interaction network of different expressed FCNs. (D,E) GO and KEGG analysis of the FCNs and correlation genes.
FIGURE 7
FIGURE 7
Correlation between FCNs and immune cell infiltration. (A,B) FCN1; (C,D) FCN2; (E,F) FCN3.
FIGURE 8
FIGURE 8
Correlation analysis between FCNs expresion and immunoinhibitors, immunostimulators and majorhistocompatibility complex (MHCs). (A–C) Correlation analysis between FCNs expresion and immunoinhibitors (D–F) Correlation analysis between FCNs expresion and immunostimulators. (G–I) Correlation analysis between FCNs expresion and MHCs.
FIGURE 9
FIGURE 9
Stromal and immune cell scores in LIHC. (A) FCN1; (B) FCN2; (C) FCN3; *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 10
FIGURE 10
Correlation of FCNs with tumor mutation burden (TMB) and microsatellite instability (MSI) in Pan cancer. (A,D) FCN1; (B,E) FCN2; (C,F) FCN3; *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 11
FIGURE 11
Correlation between FCNs expression and TIDE score. (A) FCN1; (B) FCN2; (C) FCN3; ***p < 0.001.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akaiwa M., Yae Y., Sugimoto R., Suzuki S. O., Iwaki T., Izuhara K., et al. (1999). Hakata Antigen, a New Member of the Ficolin/opsonin P35 Family, Is a Novel Human Lectin Secreted into Bronchus/alveolus and Bile. J. Histochem Cytochem. 47 (6), 777–785. 10.1177/002215549904700607 - DOI - PubMed
    1. Arellano-Garcia M. E., Li R., Liu X., Xie Y., Yan X., Loo J. A., et al. (2010). Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer. Ijms 11 (9), 3106–3121. 10.3390/ijms11093106 - DOI - PMC - PubMed
    1. Endo Y., Matsushita M., Fujita T. (2007). Role of Ficolin in Innate Immunity and its Molecular Basis. Immunobiology 212 (4-5), 371–379. 10.1016/j.imbio.2006.11.014 - DOI - PubMed
    1. Feng G.-S., Hanley K. L., Liang Y., Lin X. (2021). Improving the Efficacy of Liver Cancer Immunotherapy: The Power of Combined Preclinical and Clinical Studies. Hepatol. Baltim. Md 73 (Suppl. 1), 104–114. 10.1002/hep.31479 - DOI - PMC - PubMed
    1. Fujimori Y., Harumiya S., Fukumoto Y., Miura Y., Yagasaki K., Tachikawa H., et al. (1998). Molecular Cloning and Characterization of Mouse Ficolin-A. Biochem. Biophysical Res. Commun. 244 (3), 796–800. 10.1006/bbrc.1998.8344 - DOI - PubMed