Pan-Cancer Analysis of the Prognostic and Immunological Role of SEMA7A

Abstract

Background: Semaphorin7A (SEMA7A) has been found to regulate both nerve and vessel homeostasis, but its specific role in pan-cancer remains uncertain. This research seeks to delve into the function and clinical relevance of SEMA7A in pan-cancer.

Methods: Through an analysis of gene expression omnibus and the cancer genome atlas datasets, we investigated the impact of SEMA7A on prognosis and immune regulation across 33 types of tumors. Variations in SEMA7A expression were observed between cancerous and adjacent normal tissues, with a notable correlation between SEMA7A levels and patient prognosis.

Results: Across most cancer types, SEMA7A expression was linked to the infiltration of immune cells, as well as immune checkpoints and other immune regulators. The findings were further confirmed through quantitative real-time polymerase chain reaction analysis of SEMA7A expression in breast cancer. Further, SEMA7A is positively associated with prognosis in different cancers. Additionally, SEMA7A expression was associated with TMB and MSI in some cancer types, while in 15 types of cancer, there was a correlation between SEMA7A expression and DNA methylation. SEMA7A was associated with the expression of multiple immune checkpoint genes and abundance of tumor-infiltrating immune cells across multiple types of cancer.

Conclusion: This inaugural pan-cancer examination of SEMA7A sheds light on its prognostic and immunological significance in diverse tumor types, suggesting its potential utility as a biomarker for predicting unfavorable outcomes and immune cell infiltration in cancer.

Keywords: SEMA7A; immune cell infiltration; pan-cancer; prognosis.

Figure 1

Differential expression of SEMA7A in pan-cancer. (A) Expression of SEMA7A in tumors and normal tissues in unpaired sample analysis from TCGA database and GTEx dataset. (B) Expression of SEMA7A in tumors and normal tissues in unpaired sample analysis from TCGA database. (C) Paired sample analysis of SEMA7A mRNA expression between 18 cancers and para-cancerous tissues from the TCGA and GTEx databases. (D) The correlation between SEMA7A expression and cancer stages, including stage I, stage II, stage III, and stage IV of BLCA, KICH, KIRC, KIRP, PAAD, SKCM and THCA were investigated based on the TCGA data. (E) Comparison of SEMA7A mRNA expression levels between normal breast tissue and tumor tissues. (F) Relative expression levels of SEMA7A mRNA in BC cells and a normal breast cell line. *P<0.05, **P<0.01, ***P<0.001 vs normal.

Figure 2

Diagnostic value of SEMA7A for GBM (A), ESCC (B), ESAD (C), BLCA (D), CHOL (E), BRCA (F), UCEC (G), THCA (H), ESAD (I), KIRC (J), COAD (K), PRAD (L), CESC (M), PAAD (N), OSCC (O), LUSC (P), LUAD (Q), LIHC (R), KIRP (S), KICH (T), HNSC (U), CESC (V), STAD (W) and READ (X) using ROC curve.

Figure 3

Relationship of SEMA7A with methylation. (A) Promoter methylation level of SEMA7A in BLCA, BRC, UCEC, CESC, COAD, READ, PRAD, LUSC, LUAD, CESC, KIRP, KIRC and ESCA. (B) Correlation of SEMA7A expression with common RNA methylation types such as M6A, M5C, and M1A. *P<0.05, ***P<0.001 vs normal.

Figure 4

The mutation character of SEMA7A in pan-cancer. (A) Alteration frequency of SEMA7A in pan-cancer. (B) Mutation diagram of SEMA7A across protein domains. (C) The alteration frequency of mutation type was displayed.

Figure 5

Prognosis value of SEMA7A in pan-cancer. Forest plots of disease-free interval (A), progression-free interval (B), overall survival (C), and disease-special survival (D) comparing high and low SEMA7A expression cohorts were performed by SangerBox online website. P < 0.05 is defined as significant.

Figure 6

SEMA7A-related gene enrichment analysis. (A) The top 20 Kyoto Encyclopedia of Genes and Genomes pathways were identified using Metascape. (B) The top 20 biological processes were enriched using Metascape. (C) STRING database PPI map.

Figure 7

Correlation between the SEMA7A gene expression and TMB and MSI in pan-cancer. (A) A stick chart shows the relationship between the SEMA7A gene expression and TMB in diverse tumors. The red curve represents the correlation coefficient, and the blue value represents the range. (B) A stick chart shows the association between the SEMA7A gene expression and MSI in diverse tumors.

Figure 8

Correlation analysis between SEMA7A expression and (A and B) T cell, (C) B cell and (D) macrophage γdelta.

Figure 9

Correlation analysis between SEMA7A expression and Immune Moderator genes. *P<0.05.

Figure 10

Correlation analysis between SEMA7A expression and immune checkpoints. *P<0.05.

Figure 11

Correlation of SEMA7A expression with ImmuneScore (A), StromalScore (B), and ESTIMATEScore (C) in various cancers.