ZC3H15 in human tumors: a pan-cancer exploration of its clinical significance, molecular function, and association with the tumor immune microenvironment
5 affiliations
- 1Department of Vascular Surgery, Shanghai East Hospital, Tongji University School of Medicine
- 2The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University
- 3School of Life Science and Technology, Tongji University
- 4Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University
- 5Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University
Abstract
Background: Zinc finger CCCH-type protein 15 (ZC3H15) is a ribosome-associated eukaryotic protein involved in many biological processes, including gene expression regulation, translation, and immune modulation. Although ZC3H15 has been implicated in the development of certain tumors, its expression, functional relevance, diagnostic potential, and prognostic value in a pan-cancer context remain not fully elucidated. This study conducts an integrative, systematic, and comparative analysis of ZC3H15 across 33 cancer types and subsequently provides further experimental validation in liver cancer.
Methods: mRNA expression data of ZC3H15 were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Protein level validations were performed using the Human Protein Atlas (HPA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The cBioPortal database was used to analyze the genomic alteration of ZC3H15. Two pathway enrichment analysis methods were conducted to explore the biological functions and molecular mechanisms of ZC3H15 in pan-cancer.
Results: The results indicated that ZC3H15 was overexpressed in a wide range of tumors. In certain cancers, particularly LIHC, LUAD, BRCA, LUSC, and HNSC, its expression was significantly correlated with poor patient prognosis. Mutations and amplifications were the most common gene alterations in ZC3H15. The GSCA database showed that methylation levels were reduced in most tumor types. Abnormal expression of ZC3H15 was related to immune cell infiltration. Gene enrichment analysis indicated that ZC3H15-related genes involved in tumor progression were significantly enriched in multiple cell cycle processes. We demonstrated that knockdown of ZC3H15 suppressed cell proliferation, migration, and invasion in two liver cancer cell lines, MHCC97H and Huh7, and two BRCA cell lines, MDA-MB-231 and Hs 578T. To further clarify the functional mechanism, subsequent immunofluorescence staining confirmed that ZC3H15 knockdown induced prometaphase arrest in MHCC97H and Huh7 liver cancer cells.
Conclusions: Overall, this pan-cancer study demonstrates that ZC3H15 serves as a potential biomarker for cancer diagnosis, prognosis, and immune cell infiltration.
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BibTeX
@article{zhou2026zc3h15,
title = {{ZC3H15 in human tumors: a pan-cancer exploration of its clinical significance, molecular function, and association with the tumor immune microenvironment}},
author = {Bin Zhou and Jian Huang and Qifei Tao and Zhejin Sheng and Fabiao Zhang and Beige Jiang and Limei Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1901516},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1901516/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ZC3H15 in human tumors: a pan-cancer exploration of its clinical significance, molecular function, and association with the tumor immune microenvironment
AU - Bin Zhou
AU - Jian Huang
AU - Qifei Tao
AU - Zhejin Sheng
AU - Fabiao Zhang
AU - Beige Jiang
AU - Limei Li
PY - 2026
DA - 2026/10/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1901516
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1901516/full
AB - Background: Zinc finger CCCH-type protein 15 (ZC3H15) is a ribosome-associated eukaryotic protein involved in many biological processes, including gene expression regulation, translation, and immune modulation. Although ZC3H15 has been implicated in the development of certain tumors, its expression, functional relevance, diagnostic potential, and prognostic value in a pan-cancer context remain not fully elucidated. This study conducts an integrative, systematic, and comparative analysis of ZC3H15 across 33 cancer types and subsequently provides further experimental validation in liver cancer. Methods: mRNA expression data of ZC3H15 were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Protein level validations were performed using the Human Protein Atlas (HPA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The cBioPortal database was used to analyze the genomic alteration of ZC3H15. Two pathway enrichment analysis methods were conducted to explore the biological functions and molecular mechanisms of ZC3H15 in pan-cancer. Results: The results indicated that ZC3H15 was overexpressed in a wide range of tumors. In certain cancers, particularly LIHC, LUAD, BRCA, LUSC, and HNSC, its expression was significantly correlated with poor patient prognosis. Mutations and amplifications were the most common gene alterations in ZC3H15. The GSCA database showed that methylation levels were reduced in most tumor types. Abnormal expression of ZC3H15 was related to immune cell infiltration. Gene enrichment analysis indicated that ZC3H15-related genes involved in tumor progression were significantly enriched in multiple cell cycle processes. We demonstrated that knockdown of ZC3H15 suppressed cell proliferation, migration, and invasion in two liver cancer cell lines, MHCC97H and Huh7, and two BRCA cell lines, MDA-MB-231 and Hs 578T. To further clarify the functional mechanism, subsequent immunofluorescence staining confirmed that ZC3H15 knockdown induced prometaphase arrest in MHCC97H and Huh7 liver cancer cells. Conclusions: Overall, this pan-cancer study demonstrates that ZC3H15 serves as a potential biomarker for cancer diagnosis, prognosis, and immune cell infiltration.
SN - 1664-3224
ER -