ncRNA-mediated suppression of PRKCB drives an aggressive tumor microenvironment and poor prognosis in lung adenocarcinoma through multi-omics integration

Lung adenocarcinoma (LUAD) is characterized by high incidence and lethality. Protein kinase C, beta (PRKCB) is involved in diverse biological processes including cell proliferation, inflammation, and immunity. Despite this, the precise role of PRKCB in LUAD remains elusive. Using the UCSC pan-cancer datasets ( n = 15776), The Cancer Genome Atlas TCGA-LUAD ( n = 539), and twenty-four Gene Expression Omnibus GEO datasets, we systematically analyzed the expression and prognostic value of PRKCB. Utilizing Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and Gene Set Variation Analysis (GSVA), we uncovered potential mechanisms of PRKCB in LUAD. Furthermore, single-sample GSEA and ESTIMATE algorithms were employed to evaluate the infiltration of immune cells by PRKCB. Single-cell and spatial transcriptomic analyses identified PRKCB-associated cell-cell communication and its enrichment in non-malignant regions. Drug sensitivity analyses were conducted using the “pRRophetic” tool, and predictions on the potentially regulated microRNAs and long non-coding RNAs upstream of PRKCB were made through multiple prediction sites. The analysis revealed downregulation of PRKCB in LUAD, with patients exhibiting lower PRKCB levels associating with poorer overall survival (OS) and disease-specific survival (DSS). Enrichment analyses identified a close relationship between PRKCB and immune-related processes, with an increase in immune cell infiltration linked to elevated PRCKB expression. Integrating single-cell and spatial transcriptomic analyses, we found that PRKCB is predominantly enriched in specific immune-stromal cells within the tumor microenvironment and spatially localized to non-malignant regions. The cell–cell communication analysis revealed that PRKCB⁺ malignant cells exhibited enhanced incoming and outgoing signaling activities, particularly through the CypA, SPP1, PTN, and MIF pathways, suggesting their pivotal role in regulating intercellular communication and remodeling the immune microenvironment in LUAD. The use of the Cox regression model suggested PRKCB could be an independent prognostic factor for patients’ OS and DSS. At last, we identified a putative upstream regulatory axis of PRKCB involving AL139383.1/SH3BP5-AS1 - has-miR-9-5p. This research highlights PRKCB as a promising therapeutic target for LUAD patients.