Abstract
Background: Low molecular weight protein tyrosine phosphatase (LMWPTP), encoded by the ACP1 gene, has been implicated in tumor progression across multiple malignancies. While its oncogenic functions have been reported in colorectal cancer (CRC), its role in gastric cancer (GC) remains poorly defined. This study investigated the expression patterns, functional relevance, and prognostic impact of LMWPTP in GC, with comparative analyses in CRC. Methods: Gene expression, immune infiltration, and survival analyses were performed using data from The Cancer Genome Altas (TCGA). LMWPTP protein expression was evaluated in a gastric cancer tissue microarray. Functional assays were conducted in GC and CRC cell lines with CRISPR-Cas9-mediated LMWPTP knockout. Results: ACP1 mRNA expression was significantly upregulated in both GC and CRC compared with adjacent normal tissues. In GC, high LMWPTP expression was associated with poor differentiation in intestinal-type tumors and reduced survival in diffuse-type cases. ACP1 overexpression correlated with an elevated tumor mutation burden but a decreased cytotoxic lymphocyte infiltration signature in GC, indicating a potential relationship between ACP1 expression, tumor mutational load, and tumor immune microenvironment. Functional assays in vitro showed that LMWPTP knockout reduced migration in both GC and CRC cells, whereas a decrease in invasion was observed only in CRC cells. These findings indicate context-dependent contributions of LMWPTP to gastrointestinal tumor biology. Conclusion: LMWPTP is consistently upregulated in gastric and colorectal cancers and exhibits tumor-type-specific functional and immune associated features. These findings highlight its distinct oncogenic role and potential as a biomarker and therapeutic target in GC.