Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores

Yi Zhu; Yuan Zhou; HongGang Jiang; ZhiHeng Chen; BoHao Lu

doi:10.7717/peerj.12452

Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores

PeerJ. 2021 Nov 19:9:e12452. doi: 10.7717/peerj.12452. eCollection 2021.

Authors

Yi Zhu¹, Yuan Zhou¹, HongGang Jiang¹, ZhiHeng Chen¹, BoHao Lu¹

Affiliation

¹ Department of Gastrointestinal Surgery, The Affiliated Hospital of Jiaxing University, Jiaxing, China.

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignancies.An early diagnosis and an accurate prognosis are major focuses of CRC research. Tumor microenvironment cells and the extent of infiltrating immune and stromal cells contribute significantly to the tumor prognosis.

Methods: Immune and stromal scores were calculated based on the ESTIMATE algorithm using the sample expression profile of the The Cancer Genome Atlas (TCGA) database. GSE102479 was used as the validation database. Differentially expressed genes whose expression was significantly associated with the prognosis of CRC patients were identified based on the immune matrix score. Survival analysis was conducted on the union of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed using the STRING database to identify the closely connected modules. To conduct functional enrichment analysis of the relevant genes, GO and KEGG pathway analyses were performed with Cluster Profiler. Pivot analysis of the ncRNAs and TFs was performed by using the RAID2.0 database and TRRUST v2 database. TF-mRNA regulatory relationships were analyzed in the TRRUST V2 database. Hubgene targeting relationships were screened in the TargetScan, miRTarBase and miRDB databases. The SNV data of the hub genes were analyzed by using the R maftools package. A ROC curve was drawn based on the TCGA database. The proportion of immune cells was estimated using CIBERSORT and the LM22 feature matrix.

Results: The results showed that the matrix score was significantly correlated with colorectal cancer stage T. A total of 789 differentially expressed genes and 121 survival-related prognostic genes were identified. The PPI network showed that 22 core genes were related to the CRC prognosis. Furthermore, four ncRNAs that regulated the core prognosis genes, 11 TFs with regulatory effects on the core prognosis genes, and two drugs, quercetin and pseudoephedrine, that have regulatory effects on colorectal cancer were also identified.

Conclusions: We obtained a list of tumor microenvironment-related genes for CRC patients. These genes could be useful for determining the prognosis of CRC patients. To confirm the function of these genes, additional experiments are necessary.

Keywords: Colorectal cancer; Immune scores; Prognosis; Tumor micro-environment.

Grants and funding

This work was supported by the Basic Public Welfare Research Program of Zhejiang Province, China (LGF18H160033), the Medical and Health Science and Technology Project of Zhejiang Province, China (2019KY214), the Medical and Health Science and Technology Project of Zhejiang Province, China (2019KY692), Project of Public Welfare research of Jiaxing (2019AD32257), and the Jiaxing Key Discipline of Medicine-Oncology (Supporting Subject) (2019-zc-11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.