The value of Protein Phosphatase Methylesterase 1 in diagnosis, prognosis and immunoregulation: from pan-cancer analysis to breast cancer verification

TL;DR

This study explores PPME1's role in various cancers, showing it promotes tumor growth and could be a target for breast cancer treatment.

Contribution

The study identifies PPME1 as a potential oncogenic driver and therapeutic target in breast and other cancers through pan-cancer and functional analyses.

Findings

PPME1 is upregulated in most cancers and linked to poor prognosis in several cancer types.

PPME1 suppression inhibits breast cancer cell migration, invasion, and tumor growth.

PPME1 affects tumor microenvironment and immune response, altering anti-tumor immunity.

Abstract

The Protein Phosphatase Methylesterase 1 (PPME1) is a methylesterase specific to phosphatase 2A, a tumor suppressor, and plays a key role in tumor development. Its impact on pan-cancer diagnosis, prognosis, and immune regulation is still uncertain.

We analyzed PPME1 expression across multiple carcinomas using TCGA, GEO, and other datasets, focusing on its transcriptional profile, prognostic value, genetic and epigenetic alterations, and immunological role. To substantiate our findings, we evaluated PPME1 expression and protein levels in breast cancer tissues through RT-qPCR, Western blotting, and immunohistochemical techniques. The role of PPME1 in tumor progression was evaluated in vitro using CCK-8, colony formation, wound healing, and Matrigel transwell assays, and in vivo using xenograft tumor models.

Our pan-cancer analysis demonstrates that PPME1 is upregulated in the majority of tumors and exhibits heterogeneous expression across immune and molecular subtypes. Elevated levels of PPME1 constitute an independent risk factor in various cancers, including BLCA, BRCA, HNSC, KICH, LIHC, and UVM, and are associated with a poor prognosis. It has moderate to high diagnostic accuracy and can impact the tumor microenvironment by modifying genomic stability, affecting immunotherapy outcomes, and altering the immune response from anti-tumor to tumor-promoting. Functional enrichment analysis indicates PPME1’s involvement in DNA damage and repair, pathway activation, substance metabolism, protein modification, and immune regulation. In breast cancer, PPME1 mRNA and protein levels are elevated in tumor tissues compared to adjacent normal tissue. Functional experiments revealed that suppression of PPME1 significantly inhibits the migration, invasion, and tumor growth of breast cancer cells, suggesting that PPME1 may serve as a potential therapeutic target for breast cancer progression.

Overall, our data indicate that PPME1 acts as an oncogenic driver in multiple cancer types, promoting BRCA progression by enhancing pro-tumorigenic pathways.

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