Bioinformatics analysis of PBLD as a potential biomarker in pan-cancer and colon adenocarcinoma

Malignancies are the leading cause of global mortality, necessitating new biomarkers and therapeutic targets. Phenazine biosynthesis-like protein domain-containing protein (PBLD) has demonstrated tumor-suppressive activity in gastric and liver cancers, although its pan-cancer function remains elusive. In this study, we performed bioinformatics analysis of PBLD in pan-cancer and colon adenocarcinoma (COAD) to explore its potential role, aiming to provide new insights for cancer diagnosis and treatment.

This study systematically investigated the expression of PBLD patterns, its prognostic value, genomic alterations, associations with the tumor microenvironment (TME), and drug sensitivity in cancers, with a focus on COAD. This study performed integrated database analyses using Human Protein Atlas (HPA), Genotype Tissue Expression (GTEx), and Tumor Immune Estimation Resource version 2.0 (TIMER2.0) for normal/tumor expression; Gene Expression Profiling Interactive Analysis (GEPIA2) and Gene Set Cancer Analysis (GSCA) for survival and pathological staging; and cBioPortal for genetic alterations. Correlation analyses were performed to assess associations with tumor mutational burden (TMB)/microsatellite instability (MSI), immune infiltration (TIMER2.0, Spearman), and drug responsiveness [Genomics of Drug Sensitivity in Cancer (GDSC)/Cancer Therapeutics Response Portal (CTRP) through GSCA]. Functional enrichment [Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/Gene Set Enrichment Analysis (GSEA)], and protein-network analysis (STRING) were also conducted.

PBLD was significantly downregulated in 14 cancers, notably in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), COAD, esophageal carcinoma (ESCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung squamous cell carcinoma (LUSC), and rectum adenocarcinoma (READ), and was associated with a poor prognosis. Its expression was correlated with TMB/MSI, immune cell infiltration, and drug sensitivity. Enrichment analyses revealed the important role of PBLD in the amino acid and lipid metabolism pathways. COAD-specific analyses further identified associations among suppressed PBLD expression, metabolic dysregulation, immune activation, and epigenetic silencing.

These findings establish PBLD as a pan-cancer prognostic biomarker with mechanistic links to metabolism and immune modulation, supporting its potential role for precision cancer management.