Pan-Cancer Landscape Of PRKD3: Integrative TCGA Multi-Omics Analysis

03 Apr 20264 min read0 viewsJournal Feed

GIST

by Jocshan Loaiza-Moss, Michael Leitges Cancer remains a leading cause of mortality worldwide and a significant barrier to improving quality of life across all populations. The protein kinase D family, including PRKD3 , has been demonstrated to play a crucial role in cancer development through its involvement in regulating key cellular processes.

Although growing evidence highlights the role of PRKD3 in the tumorigenesis of certain cancers, a comprehensive pan-cancer analysis of PRKD3 remains unavailable. To address this, we performed an integrative pan-cancer analysis of PRKD3 using multi-omics datasets from The Cancer Genome Atlas, the Genotype-Tissue Expression project, and cBioPortal.

We examined PRKD3 expression, copy number variation, mutation, and DNA methylation, and evaluated their associations with clinicopathological features, patient survival, and diagnostic potential across 33 cancer types. Immune relevance was further assessed through correlations with immune infiltration, checkpoint gene expression, and immunotherapy response-related genomic biomarkers.

Our results revealed that PRKD3 expression was highly heterogeneous, showing significant upregulation in liver cancer, gastric cancer, and adrenocortical carcinoma, and downregulation in others.

Clinical Editorial

Contextual framing and study rationale

Immune-related dimensions are explored via correlations with immune infiltration, checkpoint genes, and biomarkers linked to immunotherapy responses.

The report undertakes a comprehensive, integrative pan-cancer examination of PRKD3 using multi-omics data from TCGA, GTEx, and cBioPortal to elucidate expression, genomic alterations, methylation, and their associations with clinicopathological features and survival across 33 cancer types.

Study design and datasets

The analysis integrates expression, copy number variation, mutation, and DNA methylation profiles with clinical and survival data.
Immune-context assessments include relationships between PRKD3 patterns and immune checkpoint molecules as well as genomic indicators of immunotherapy responsiveness.

Key expression landscape and prognostic signals

PRKD3 exhibits marked heterogeneity across cancer types.
Significant upregulation is observed in liver cancer, gastric cancer, and adrenocortical carcinoma.
Downregulation is reported in multiple other tumors, indicating a broad and uneven expression pattern.

Associations with prognosis and tumor microenvironment

Higher PRKD3 expression generally associates with poorer prognosis in several contexts, notably liver, stomach, and adrenocortical carcinoma.
In contrast, a paradoxical association with better outcomes is noted in kidney clear cell carcinoma.
Elevated PRKD3 expression aligns with increased infiltration by stromal components, neutrophils, and cancer-associated fibroblasts in adrenocortical carcinoma, liver cancer, and gastric cancer, suggesting a link to a more immunosuppressive or pro-tumor microenvironment in these contexts.

Immunological and biomarker context

PRKD3 expression correlates with key immune checkpoint molecules, including PD-1, PD-L1, and CTLA-4, implying a potential immunomodulatory role compatible with immune evasion mechanisms.
Context-dependent relationships emerge between PRKD3 and tumor mutational burden (TMB) as well as microsatellite instability (MSI), indicating possible influences on tumor immunogenicity and responsiveness to checkpoint blockade therapies.

Limitations and interpretation

The findings are derived from integrative analyses of publicly available datasets and are descriptive in nature.
Context-specific effects vary by cancer type and biological milieu; causal relationships are not established within this analysis.