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Original Article | Open Access

Identification of positive cofactor 4 as a diagnostic and prognostic biomarker associated with immune infiltration in hepatocellular carcinoma

Liangliang Baia,b,1, Guan Liub,1, Gang Douc,1, Xiaojun Heb, Chenyu Gongc, Hongbin Zhangb, Kai Tanb( ), Xilin Dub( )
School of Medicine, Yan'an University, Yan'an 716000, China
Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China
Xi'an Medical University, Xi'an 710068, China

1 Liangliang Bai, Guan Liu, and Gang Dou contributed equally to this work.

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Abstract

Background and aims

Human positive cofactor 4 (PC4) is associated with the development and therapeutic resistance of several malignancies. However, the role of PC4 in hepatocellular carcinoma (HCC) remains obscure.

Methods

The expression status of PC4 was explored in Gene Expression Omnibus and The Cancer Genome Atlas datasets. Subsequently, the prognostic and diagnostic significance of PC4 in HCC patients was analyzed. Functional enrichment analyses were conducted to explore biological functions and potential mechanisms. The CIBERSORT algorithm was used for immune infiltration analysis. The risk signature was constructed by LASSO-Cox regression and was validated with the International Cancer Genome Consortium dataset. Quantitative real-time polymerase chain reaction was used to verify the expression levels of all genes. Tumor Immune Dysfunction and Exclusion analysis evaluated immunotherapy response. Finally, using online databases, PC4-related competing endogenous RNA networks were constructed.

Results

PC4 levels were significantly upregulated in HCC and positively correlated with the pathological grade and clinical stage. The PC4-high expression group showed worse prognosis. In addition, PC4 could distinguish between tumor and normal tissues with an area under the curve of 0.965. The PC4 level was associated with immune checkpoints and immune cell infiltration. In the training and validation sets, the eight-gene risk signature strongly correlated with HCC patient prognosis. Tumor Immune Dysfunction and Exclusion analysis showed that patients in both the PC4-low and low-risk groups were more likely to benefit from immunotherapy. Finally, an lncRNA/microRNA-101-3p/PC4 network was constructed.

Conclusion

We confirmed PC4 as a diagnostic and prognostic biomarker in HCC patients. We also developed and validated an eight-gene risk signature, which will help in clinical decision-making. The competing endogenous RNA network could help explore the regulatory mechanisms of PC4 in HCC.

Keywords

Hepatocellular carcinomaPrognosisRisk signatureHuman positive cofactor 4

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iLIVER
Volume 2 Issue 4,
December 2023
Pages 188-201
DOI: 10.1016/j.iliver.2023.08.007
Cite this article:
Bai L, Liu G, Dou G, et al. Identification of positive cofactor 4 as a diagnostic and prognostic biomarker associated with immune infiltration in hepatocellular carcinoma. iLIVER, 2023, 2(4): 188-201. https://doi.org/10.1016/j.iliver.2023.08.007

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Received: 09 July 2023
Revised: 15 August 2023
Accepted: 22 August 2023
Published: 15 September 2023
© 2023 The Authors. Tsinghua University Press.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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