The role of PCMT1 in prognosis tumor immune microenvironment and therapeutic responses across cancers

Our plain-English summary of The role of PCMT1 in prognosis tumor immune microenvironment and therapeutic responses across cancers, by B. Wang, S. Huang, R. Ren, et al (Discover Oncology, 2026).

The study

• Authors: B. Wang, S. Huang, R. Ren, R. Yao, E. Kou, H. Zhao, H. Zhu, M. Zhang, L. Wang, Y. Zhu
• Journal: Discover Oncology
• Published: 2026;17(1):257
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Emerging evidence highlights the overexpression of Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) in multiple malignancies. However, its pan-cancer prognostic significance, tumor immune microenvironment (TIME) interactions, and therapeutic implications remain underexplored.

Methods: Multi-omics data were integrated from UCSC Xena, GTEx, UALCAN, and published cohorts. PCMT1 expression patterns were systematically analyzed across 33 cancer types. Associations between PCMT1 and clinical outcomes, immune infiltration, immune checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity were evaluated using bioinformatics pipelines.

Results: Our pan-cancer analysis revealed differential expression patterns of PCMT1 across various malignancies, with significant upregulation in 20 cancer types and downregulation in 3 cancer types. Notably, PCMT1 overexpression was predominantly observed in epithelial-origin tumors, such as ACC (adrenocortical carcinoma), BRCA (breast invasive carcinoma), COAD (colon adenocarcinoma), and LUAD (lung adenocarcinoma). Survival analysis demonstrated that elevated PCMT1 expression was significantly correlated with unfavorable prognosis in multiple epithelial tumors, particularly in BRCA, esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), and mesothelioma (MESO). Furthermore, comprehensive analysis identified significant associations between PCMT1 expression and various tumor microenvironment features, including immune scores, six distinct immune cell types, four immunosuppressive cell populations, cancer-associated fibroblasts (CAFs)-related markers, and immunosuppressive factors. PCMT1 expression also showed significant correlations with tumor mutation burden (TMB), microsatellite instability (MSI), DNA stemness score (DNAss), and RNA stemness score (RNAss). Particularly noteworthy was the strong positive correlation between PCMT1 expression and CAFs infiltration, along with their associated factors. These findings were further validated in independent immunotherapy cohorts, where PCMT1 consistently demonstrated immunosuppressive characteristics.

Conclusion: Multi-omics analysis suggests that PCMT1 may serve as a potential prognostic biomarker and a novel immunotherapy target for pan-cancer.

© 2026. The Author(s).

In plain English

This was a computer-based analysis of public cancer databases. It looked at a gene called PCMT1 across 33 cancer types, one of which was mesothelioma (labelled MESO). The article does not discuss asbestos or any asbestos exposure. The authors compared PCMT1 expression levels in tumors with normal tissue and split patients into high and low PCMT1 groups at the median. PCMT1 differed between tumor and normal tissue in 23 of 33 tumor types. Higher PCMT1 was linked to worse overall survival in five cancers, including mesothelioma, and to worse disease-specific survival in six cancers, again including mesothelioma. PCMT1 was also linked to immune-suppressing cells around tumors and to drug responses in cancer cell lines and patient groups. The authors concluded that PCMT1 "may serve as a potential prognostic biomarker" and a possible target for immunotherapy. They noted that their study shows correlations rather than causes. They also noted that it used retrospective public data, which may introduce selection bias.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Pan-cancer bioinformatics analysis of publicly available databases (no new patients or experiments)
• Who was studied: Tumor data for 33 human cancer types, including mesothelioma (MESO), from UCSC Xena/TCGA, with normal tissue from GTEx; patient numbers are not given in the text
• Exposure: Not asbestos. The factor studied was PCMT1 gene expression, with patients in each cancer type split into high and low groups at the median
• Main results:
  • PCMT1 RNA levels differed between tumor and normal tissue in 23 of 33 tumor types
  • PCMT1 was lower in two epithelial-origin tumors, cholangiocarcinoma (CHOL) and kidney renal clear cell carcinoma (KIRC)
  • At the protein level, PCMT1 was significantly lower in tumor than in normal tissue for 10 tumor types, which did not match the RNA findings
  • Higher PCMT1 predicted poor overall survival in breast, esophageal, head and neck, liver cancer and mesothelioma (no hazard ratios printed in the text)
  • Higher PCMT1 predicted poor disease-specific survival in six cancers, including mesothelioma
  • Higher PCMT1 was associated with better prognosis in KIRC, LGG, READ and THYM
  • PCMT1 was associated with four immune-suppressing cell types. In mesothelioma and three other cancers it correlated positively with M0 macrophages
  • In patient groups that received chemotherapy, breast cancer and glioblastoma patients with higher PCMT1 had greater chemotherapy benefit
  • In immunotherapy groups, GBM and KIRC patients with higher PCMT1 showed resistance to PD-1 immunotherapy
• The authors' conclusion: The authors concluded that PCMT1 may be a potential prognostic biomarker and a possible target for improving immunotherapy, particularly through cancer-associated fibroblasts and immunosuppressive pathways
• Limitations the authors state:
  • All analyses used publicly available retrospective datasets, which may introduce selection bias
  • Expression came from bulk RNA sequencing, without single-cell or spatial detail
  • Immune infiltration was estimated by computer algorithms, which are inferential
  • The study shows correlations, not causes

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Microsatellite Instability (MSI-H), Carcinoma, Adenocarcinoma, Lung Adenocarcinoma, Squamous Cell Carcinoma, Mesothelioma, Tumor Microenvironment.

Related studies

• Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types — T. van den Ende, H.G. van den Boorn, et al. (2020)
• Unraveling tumor microenvironment heterogeneity in malignant pleural mesothelioma identifies biologically distinct immune subtypes enabling prognosis determination — K. Yang, T. Yang, et al. (2022)
• Tumor Microenvironment-Associated Immune-Related Genes for the Prognosis of Malignant Pleural Mesothelioma — X. Xu, L. Cheng, et al. (2020)
• Reprogramming the tumor microenvironment in mesothelioma: from immune suppression to therapeutic opportunity — L. Cerbone, A. Garau, et al. (2026)
• BAP1 Deficiency Inflames the Tumor Immune Microenvironment and Is a Candidate Biomarker for Immunotherapy Response in Malignant Pleural Mesothelioma — D. Xu, Y. Gao, et al. (2024)
• Cyclin Pathway Genomic Alterations Across 190,247 Solid Tumors: Leveraging Large-Scale Data to Inform Therapeutic Directions — D.L. Jardim, S.Z. Millis, et al. (2021)

Browse more research in Discover Oncology, or return to medical research.