Work

Pan-cancer multi-omics analysis reveals IQCE as a malignant cell-restricted oncogenic biomarker driving immunosuppression and chemoresistance in cutaneous melanoma

Year: 2025

Type: article

Abstract: BACKGROUND: Cutaneous melanoma (SKCM) presents significant therapeutic challenges due to heterogeneity and acquired resistance to targeted and immune checkpoint blockade therapies. IQCE, a ciliary scaffold protein, has poorly defined roles in cancer. Its clinical significance, molecular mechanisms, and impact on the tumor microenvironment (TME) and therapy response are largely unknown. METHODS: We conducted a comprehensive pan-cancer multi-omics analysis of IQCE using genomic, transcriptomic, proteomic, spatial transcriptomic, single-cell transcriptomic, and pharmacogenomic datasets. Analyses included differential expression, survival, pathway enrichment, immune deconvolution, cellular localization, and drug sensitivity prediction. RESULTS: IQCE was significantly upregulated in multiple solid tumors, most notably cutaneous melanoma (SKCM), liver hepatocellular carcinoma (LIHC), and glioblastoma (GBM), demonstrating strong diagnostic value. High IQCE independently predicted poor prognosis in SKCM. Mechanistically, elevated IQCE correlated with suppression of immune pathways (e.g., cytokine signaling), inhibition of apoptosis, and activation of RAS/MAPK/RTK oncogenic signaling. Single-cell and spatial analyses confirmed IQCE enrichment specifically within malignant cells. High IQCE was associated with broad chemoresistance. Pharmacogenomic profiling revealed a consistent inverse correlation between IQCE expression and sensitivity to the p53-reactivating compound RITA. CONCLUSION: IQCE emerges as a novel oncogene-associated biomarker with significant diagnostic and prognostic utility, particularly in SKCM. It promotes an immunosuppressive TME and oncogenic signaling while being localized to malignant cells. Although associated with chemoresistance, the vulnerability of IQCE-high tumors to RITA offers a promising therapeutic strategy. IQCE represents a compelling target for precision oncology.

Source: Discover Oncology

DOI: 10.1007/s12672-025-03841-0

Authors: Qing Luo, Jingya Wang, Ting Chen, Jielong Li

Institutions: Xuzhou Medical College, The First People’s Hospital of Lianyungang, Kangda College of Nanjing Medical University, Second People’s Hospital of Huai’an, Huai'an Hospital of Huai'an City

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,690