248P - Screening zinc homeostasis-related genes identifies metallothionein 1H (MT1H) as a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC)

Background

Over the past decade, a growing body of literature has elucidated the involvement of zinc homeostasis in tumor growth and progression. Herein, we present a bioinformatics-based study to evaluate the prognostic potential of zinc homeostasis-related genes in ccRCC.

Methods

The Human Genome Atlas Program (TCGA) was accessed to retrieve level 3 omics data and the corresponding clinicopathological variables. Differential expression of zinc homeostasis-related genes were considered statistically significant with a |Log₂(fold change)| ≥ 1.5 and a P-value ≤ .01. The prognostic potential of selected genes was assessed using multivariate Cox logistic regression analysis. LinkedOmics was used to functionally annotate significantly co-expressed genes using KEGG terminology. Enrichment of the hallmarks of cancer gene sets was tested using gene set enrichment analysis (GSEA). Tumor immune microenvironment was explored using TIMER 2.0.

Results

A total of five significant differentially expressed genes were detected, including MT1G, SLC30A2, MT1F, SLC39A1, and MT1H. The latter being the only gene with a significant prognostic profile. High MT1H expression is associated with shortened overall survival (HR: 1.534, 95% CI: 1.140-2.064, P < .0048). Multivariate Cox logistic regression identified MT1H as an independent prognostic biomarker in ccRCC (HR: 1.392, 95% CI: 1.016-1.907, P < .04). MT1H co-expressed genes annotation highlighted the involvement of mineral absorption, ribosome, oxidative phosphorylation, and proteasome pathways. GSEA illustrated several alternations in epithelial-mesenchymal transition, inflammatory response,coagulation, complement, IL-6/JAK/STAT3 signaling, glycolysis, KRAS signaling, hypoxia, E2F targets, estrogen response, INF-γ signaling, and apoptosis. No clear trends or patterns were observed in tumor immune microenvironment in response to MT1H upregulation.

Conclusions

MT1H has been identified as a potential prognostic biomarker in ccRCC. Further experimental studies are needed to confirm the observed findings and to detect the exact molecular modulators involved.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.