BackgroundWAC-antisense RNA1 (WAC-AS1) is a newly identified long non-coding RNA (lncRNA) implicated in the prognosis and development of a few types of tumors. However, the correlations of WAC-AS1 with immune infiltration and patient prognosis in pan-cancer remain unclear. In the present study, we aimed to investigate the prognostic value and immunological functions of WAC-AS1 across 33 different types of cancers.MethodsTo investigate the potential oncogenic roles of WAC-AS1, bioinformatics analyses were performed using the Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEx) datasets. The correlations of WAC-AS1 with prognosis, clinical phenotype, tumor mutational burden (TMB), microsatellite instability (MSI), tumor regulation-related genes, tumor microenvironment, immune cell infiltration, and drug resistance to commonly used chemotherapy drugs in different types of tumors were explored. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to explore the biological functions of WAC-AS1 in tumors. In situ hybridization (ISH) was performed in tissue microarray (TMA) to confirm the expression of WAC-AS1 in multiple tumor tissues.ResultsWAC-AS1 showed aberrant expression in most cancers when compared to the normal tissues. It also has prognostic value in multiple types of cancers. Elevated WAC-AS1 expression was associated with poor prognosis and overall survival in adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), and liver hepatocellular carcinoma (LIHC). A significant negative correlation between WAC-AS1 expression and overall survival was observed in brain lower-grade glioma (LGG), pancreatic adenocarcinoma (PAAD), and skin cutaneous melanoma (SKCM). The expression of WAC-AS1 also showed a correlation with clinical stage in six types of tumors, and with tumor mutational burden and microsatellite instability in several different types of cancers. The immune scores of those cancers were found to be significant. Additionally, the effectiveness of fluorouracil and four other anticancer drugs was significantly different based on the expression of WAC-AS1 in these cancers. Moreover, the ISH results showed in six types of tumors, the expression of WAC-AS1 was consistent with the Pan-cancer analysis using TCGA and GTEx database.ConclusionsThese results indicate an intensive involvement of WAC-AS1 in the regulation of immune responses, immune cell infiltration, and malignant properties in various types of cancers, suggesting that WAC-AS1 may serve as a prognostic marker across diverse types of cancers.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41065-023-00290-z.