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Background Lysophosphatidic acid (LPA) and its receptors play a key role in regulating cancer progression. Upregulation of LPA receptor 2 ( LPAR2 ) plays a role in carcinogenesis; however, the exact role of  LPAR2  in tumors remains elusive. This study aims to explore the correlation between LPAR2 expression with tumor prognosis and immune infiltration in pan-cancers. Materials and methods The expression of  LPAR2  in pan-cancers was analyzed using the Online Cancer Microarray Database (Oncomine), Tumor Immune Estimation Resource (TIMER), and UALCAN databases. The effects of  LPAR2  on the clinical prognosis in pan-cancer were examined using the Kaplan–Meier plotter (KM plotter) as well as Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Human Protein Atlas (HPA) databases. Moreover, the R software program was applied for validation of expression and prognostic value of  LPAR2  in tumor patients in the Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. The relationship between the expression level of  LPAR2  and the clinical and molecular criteria of head and neck squamous cell carcinoma (HNSC) and kidney renal clear cell carcinoma (KIRC) was analyzed using UALCAN, whereas the relationship between LPAR2 expression and prognosis in patients with HNSC and KIRC with different clinical characteristics was examined using the KM plotter. Furthermore, the correlation between  LPAR2  expression and tumor immune infiltration was examined using TIMER. The correlation between LPAR2 expression and gene markers of tumor immune infiltrates was analyzed using TIMER and GEPIA. In addition, the cBioPortal for Cancer Genomics was used to calculate the mutations, methylations, and altered neighbor genes of  LPAR2 . Results The expression of  LPAR2  was significantly correlated with the outcome of multiple types of cancer, especially HNSC and KIRC. Furthermore, high expression of  LPAR2  was significantly associated with various immune markers in the immune cell subsets of HNSC and KIRC. Conclusions High expression of  LPAR2  plays significantly different prognostic roles in HNSC and KIRC possibly owing to its association with different immune markers.  LPAR2  is correlated with tumor immune cell infiltration and is a valuable prognostic biomarker for HNSC and KIRC. However, further experiments are required to validate these findings.

LPAR2 correlated with different prognosis and immune cell infiltration in head and neck squamous cell carcinoma and kidney renal clear cell carcinoma