Does the LHPP gene share a common biological function in pancancer progression?

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Emerging evidence suggests LHPP (histidine phosphatase) protein inhibits cancer progression.
• A comprehensive pan-cancer analysis of LHPP's role is currently unavailable.

Purpose of the Study:

• To investigate the tumor suppressive function of LHPP across 33 cancer types using bioinformatics.
• To evaluate the impact of LHPP expression on gastric cancer cell behavior and patient prognosis.

Main Methods:

• Utilized bioinformatics tools and The Cancer Genome Atlas (TCGA) project for pan-cancer analysis.
• Performed stable transfection of HGC-27 gastric cancer cells with lentiviruses to modulate LHPP expression.
• Analyzed LHPP mRNA and protein expression, overall survival (OS), disease-free survival (DFS), genetic alterations, and cancer-associated fibroblast infiltration.

Main Results:

• LHPP expression was downregulated in most cancer tissues compared to normal tissues.
• Higher LHPP expression correlated with better OS and DFS in brain glioma and renal carcinoma.
• Increased LHPP expression suppressed gastric cancer cell proliferation, migration, and invasion, reducing cell-cycle and EMT markers.
• LHPP amplification was the most frequent mutation; absence of LHPP mutation improved prognosis in UCEC, STAD, and COAD.
• Cancer-associated fibroblast infiltration was noted in specific cancers.

Conclusions:

• LHPP functions as a tumor suppressor across a wide range of cancers.
• LHPP expression levels and genetic alterations impact patient prognosis.
• LHPP represents a potential therapeutic target for various malignancies.