Potential prognostic biomarker SERPINA12: implications for hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors, exhibiting a high morbidity and mortality rate. The mechanism of its occurrence and development requires further study. The objective of this study was to investigate the role of SERPINA12 in the diagnosis, prognosis prediction and biological function within HCC.

Methods: The Cancer Genome Atlas (TCGA) data were employed to analyze the relationship between clinical features and SERPINA12 expression in HCC. Kaplan-Meier curves were utilized to analyze the correlation between SERPINA12 expression and prognosis in HCC. The function of SERPINA12 was determined by enrichment analysis, and the relationship between SERPINA12 expression and immune cell infiltration was investigated. The expression of SERPINA12 was examined in 75 patients with HCC using RT-qPCR and immunohistochemistry, and survival analysis was performed.

Results: The expression of SERPINA12 from TCGA database was found to be significantly higher in HCC tissues than in normal tissues and carried a poor prognosis. ROC curve demonstrated the diagnostic potential of SERPINA12 for HCC. The multivariate Cox regression analysis showed that pathologic T stage, tumor status, and SERPINA12 expression were independently associated with patient survival. The SERPINA12 expression was found to correlate with immune cell infiltration. Our RT-qPCR and immunohistochemical analysis revealed high expression of SERPINA12 in tumor tissues. Survival analysis indicated its association with poor prognosis.

Conclusion: SERPINA12 is a promising biomarker for diagnosis and prognosis, and it is associated with immune cell infiltration.

Keywords: Bioinformatics; Hepatocellular cancer; Prognosis; SERPINA12.

Fig. 1

SERPINA12 expression in pan-cancers from TCGA database. A Unpaired samples for tumour tissues and non-tumour tissues. B Paired samples for tumor tissues and adjacent tissues. C Expression of SERPINA12 in the unpaired group of HCC. D Expression of SERPINA12 in the paired group of HCC. significances: ns, p ≥ 0.05; *p < 0.05; **p < 0.01; ***p < 0.001

Fig. 2

Correlation of SERPINA12 expression with clinicopathologic characteristics. A pathologic stage, B histologic grade, C vascular invasion, D AFP level, e gender, ns, p ≥ 0.05; *p < 0.05; **p < 0.01; ***p < 0.001

Fig. 3

Kaplan–Meier curve and its subgroups in HCC. A Overall survival (OS), B Pathologic stage I & II, C Pathologic stage III & IV, D Tumor status: with tumor, E Histologic grade: G1&G2, F Histologic grade: G3 & G4, G Tumor status; tumor free, H BMI ≤ 25, I BMI > 25

Fig. 4

Receiver operating characteristic (ROC) curve and Nomogram for SERPINA12. The ROC curve and the area under the ROC curve was calculated. A for SERPINA12, B for AFP, C for combination of them, D Youden’s Index of SERPINA12, AFP, and combination of them, E The calibration curves of SERPINA12 for the nomogram, F Nomogram representation of the multivariate model

Fig. 5

Differential gene expression analysis of SERRPINA12. A Volcano map of differentially expressed genes, B Heat map of the top 10 most differential genes, C Enrichment analysis of SERRPINA12. KEGG, Kyoto Encyclopedia of Genes and Genomes, BP, Biological Process, CC, Cellular Component, MF, Molecular Function

Fig. 6

The protein–protein interaction network for SERPINA12 based on STRING

Fig. 7

Analysis of immune cell infiltration. A Bubble plot of the correlations between SERPINA12 expression and immune cell infiltration level, B Subgroups (high and low SERPINA12 expression groups) comparison of immune cell infiltration analysis, Significant infiltrated immune cells: C NK cells, D CD8 T cells, E Tcm, F neutrophils, G pDC, H Th2 cells, significances: ns, p ≥ 0.05; *p < 0.05; **p < 0.01; ***p < 0.001

Fig. 8

Immunohistochemical staining of SERPINA12 in HCC. A, C The adjacent tissues were magnified to 100 and 200 times under the microscope. B, D The tumor tissues were magnified to 100 and 200 times under the microscope

Fig. 9

Immunohistochemical analysis SERPINA12 in HCC. A Staining score of SERPINA12, B Chi-square test for the immunohistochemical data, C Kaplan–Meier analysis of 75 patients for overall survival, D Kaplan–Meier analysis of 75 patients progression free survival

Fig. 10

RT-qPCR analysis of SERPINA12 and immune cell marker genes mRNA expression, A the groups of tumor tissues and adjacent tissue, B the groups of high and low based on the median expression level of SERPINA12