Exploration of novel clusters and prognostic value of immune‑related signatures and identify HAMP as hub gene in colorectal cancer

Hongyuan Wu; Heling Dong; Shaofang Ren; Jianxin Chen; Yan Zhang; Meng Dai; Yinfen Wu; Xuefang Zhang

doi:10.3892/ol.2023.13946

Exploration of novel clusters and prognostic value of immune‑related signatures and identify HAMP as hub gene in colorectal cancer

Oncol Lett. 2023 Jul 5;26(2):360. doi: 10.3892/ol.2023.13946. eCollection 2023 Aug.

Authors

Hongyuan Wu^{1

2}, Heling Dong³, Shaofang Ren⁴, Jianxin Chen⁵, Yan Zhang¹, Meng Dai⁶, Yinfen Wu⁷, Xuefang Zhang^{1

2}

Affiliations

¹ Department of Radiation Oncology, Affiliated Dongguan People's Hospital of Southern Medical University, Dongguan, Guangdong 523009, P.R. China.
² Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong 523009, P.R. China.
³ School of Sports Education, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
⁴ State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
⁵ Department of General Surgery, Affiliated Dongguan People's Hospital of Southern Medical University, Dongguan, Guangdong 523009, P.R. China.
⁶ Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
⁷ Department of Oncology, Affiliated Dongguan People's Hospital of Southern Medical University, Dongguan, Guangdong 523009, P.R. China.

Abstract

Immune checkpoint inhibitors currently serve an important role in prolonging patients' overall survival. However, the prognostic signatures of immune checkpoint inhibitors in colorectal cancer (CRC) remain uncertain and more knowledge on the genetic characteristics of colorectal cancer is needed. Patients with CRC from The Cancer Genome Atlas were classified into high-immunity group and low-immunity group based on median scores from single-sample gene set enrichment analysis using the GSVA package. We explored immune status by immune scores, stromal scores and tumor purity scores in ESTIMATE package and surveyed the difference of immune cells distribution with CIBERSORT package. Eighteen genes were selected using the LASSO Cox regression method and a prognostic risk model was constructed. Compared with patients in the low-risk group, those in the high-risk group had a significantly shorter survival time. For assessment of the prognostic validity of the risk model, receiver operating characteristic curves with areas under the curve of 0.769, 0.774 and 0.771 for 1, 3 and 5 years respectively. Differences in molecular mechanisms between high- and low-risk groups were analyzed using the clusterProfiler package. Tumor Immune Dysfunction and Exclusion data were downloaded and analyzed. The top 5 enriched pathways in the high-risk group involved 'calcium signaling', 'dilated cardiomyopathy', 'extracellular matrix receptor interaction', 'hypertrophic cardiomyopathy' and 'neuroactive ligand receptor interaction'. HAMP was identified as a hub gene, which was highly expressed in tumor samples. The results of the present study indicate that the prognostic model based on both immune-related genes and HAMP has the potential to support personalized treatment.

Keywords: HAMP; colorectal cancer; immune-related signatures; prognostic value.

Grants and funding

This work was funded by the Fundamental Research Funds for the Central Universities (grant no. 21JNQN14); the Technology Development Cultivation of Program Southern Medical University (grant no. KJ20161121); Guangdong Sci-tech Commissioner (grant no. 20211800500322); the National Natural Science Foundation of China (grant no. 81803877); the Dongguan City Social Science and Technology Development (Key) Project (grant no. 202050715001207); and the Fundamental and Applied Basic Research Fund of Guangdong Province (grant no. 2020B1515120063).