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. 2024 Jan 11:10:1277508.
doi: 10.3389/fmolb.2023.1277508. eCollection 2023.

Pan-cancer analysis of SERPINE family genes as biomarkers of cancer prognosis and response to therapy

Yating Liu #  1 , Xinyu Li #  1 , Shanshan Chen  1 , Changyu Zhu  1 , Yijun Shi  1 , Shoutao Dang  1 , Weitao Zhang  1 , Wei Li  1
Affiliations

Pan-cancer analysis of SERPINE family genes as biomarkers of cancer prognosis and response to therapy

Yating Liu et al. Front Mol Biosci. .

Abstract

Background: Serine protease inhibitor E (SERPINE) family genes participate in the tumor growth, cancer cell survival and metastasis. However, the SERPINE family members role in the prognosis and their clinical therapeutic potentials in various human cancer types have not been elaborately explored. Methods: We preliminarily analyzed expression levels and prognostic values of SERPINE family genes, and investigated the correlation between SERPINEs expression and tumor microenvironment (TME), Stemness score, clinical characteristic, immune infiltration, tumor mutational burden (TMB), immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of SERPINEs from DAVID and KOBAS databases. Results: SERPINE1, SERPINE2, and SERPINE3 expression were upregulated in nine cancers, twelve cancers, and six cancers, respectively. The expression of SERPINE family genes was associated with the prognosis in several cancers from The Cancer Genome Atlas (TCGA). Furthermore, SERPINE family genes expression also had a significant relation to stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. SERPINE1 and SERPINE2 expression significantly increased in tumor advanced stage in colon adenocarcinoma (COAD). Results showed that SERPINE1 and SERPINE2 expression were negatively related with B cells and Monocytes, respectively. SERPINE2 expression had a significantly positive relation with B cells and Macrophages. In terms of TMB, SERPINE1, SERPINE2, and SERPINE3 were found to associated with TMB in seven cancers, fourteen cancers, and four cancers, respectively. Moreover, all SERPINE gene family members were significantly correlated with immune subtypes. SERPINE1 expression had a significantly positive or negative correlation with drug sensitivity. Conclusion: The study indicated the great potential of SERPINE family genes as biomarkers for prognosis and provided valuable strategies for further investigation of SERPINE family genes as potential targets in cancer.

Keywords: SERPINE family genes; bioinformatics; immune infiltration; pan-cancer; prognosis; tumor microenvironment.

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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
Differences in RNA and protein expression levels of SERPINE family genes in different tumors. (A) Boxplot illustrating the distribution of SERPINE family genes expression in various cancers. (B) Heatmap showing the difference of SERPINE family genes expression levels in different cancer types from TCGA database. The red and green indicate the high or low expression, respectively. (C) The correlation between SERPINE family genes. (D–F) The expression level of SERPINE family genes in normal and tumor tissues in human pan-cancer. (G–H) The different protein expression level in matched tumor tissues in the UALCAN database. The blue boxplots indicate the normal tissues and the red boxplots indicate the cancer tissues. Z-values represent standard deviations from the median across samples for the cancer types. (p < 0.05 was considered significant, *p < 0.05, **p < 0.01, and ***p < 0.001).
FIGURE 2
FIGURE 2
Survival analysis of SERPINE family genes across multiple cancer types. The red line in the photos indicates high expression and the blue line in the photos indicates low expression. p-value less than 0.05 is considered as difference.
FIGURE 3
FIGURE 3
Correlation analysis of SERPINE family genes expression with survival by the COX method in different types of cancers. Hazard ratio <1 represent low risk and hazard ratio >1 represent high risk. (p < 0.05 was considered significant).
FIGURE 4
FIGURE 4
Overall survival curves comparing the high and low expression of SERPINE family genes in various cancers in Kaplan-Meier Plotter database. (p < 0.05 was considered significant).
FIGURE 5
FIGURE 5
Correlation of SERPINE family genes expression with tumor microenvironment, Stemness score. The SERPINE family genes associated Stromal score (A) Immune score; (B) RNAss; (C) and DNAss (D) are illustrated. Red dots indicate a positive correlation, and blue dots indicate a negative correlation. (E–H) Correlation analysis of SERPINEs expression with Stemness score, TME in four cancer types. R means correlation value, positive number means positive correlation, negative number means negative correlation. (p < 0.05 was considered significant).
FIGURE 6
FIGURE 6
Correlation between SERPINE family genes expression and tumor stages. (A–D) Association of SERPINE family genes expression with the clinical stages in selected cancers from TCGA database. (E,F) Association of SERPINE family genes expression with the clinical stages in selected cancers from GEO database. (p < 0.05 was considered significant, *p < 0.05, **p < 0.01, and ***p < 0.001).
FIGURE 7
FIGURE 7
Association of SERPINE family genes expression with immune infiltration, TMB and immune subtype in different cancer types. R > 0.5, p < 0.05. (A) The correlation between SERPINEs and immune infiltration. (B) The correlation between SERPINEs and TMB. (C) SERPINE family genes expression levels of different immune subtype in pan-cancer. X-axis represents immune subtype, Y-axis represents gene expression. C1, wound healing; C2, IFN-γ dominant; C3, inflammatory; C4, lymphocyte depleted; C5, immunologically quiet; C6, TGF-β dominant. (p < 0.05 was considered significant, *p < 0.05, **p < 0.01, and ***p < 0.001).
FIGURE 8
FIGURE 8
Functional and pathway annotation of SERPINE family genes in pan-cancer. (A) SERPINE1 related diseases network. (B) SERPINE2 related diseases network. (C) SERPINE3 related diseases network. (D) GO enrichment analysis from DAVID database. (E) GO enrichment analysis from KOBAS database. (F) Pathway analysis from KOBAS database. (G) Diseases analysis from KOBAS database. (H) SERPINE1-binding proteins in HNSC from STRING database. (I) SERPINE1-binding proteins in COAD from STRING database. (J) SERPINE1-binding proteins in BRCA from STRING database.
FIGURE 9
FIGURE 9
Drug sensitivity analysis of SERPINE family genes. Cor, correlation coefficient.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by Beijing Municipal Science and Technology Commission (No. Z 221100007422026).