A systematic review verified by bioinformatic analysis based on TCGA reveals week prognosis power of CAIX in renal cancer

BACKGROUND: Carbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with some tumors such as head and neck carcinoma. But renal cell carcinoma is an exception. The prognostic value of CAIX in RCC used to be associated with patients’ survival according to published works. This study aimed to rectify the former conclusion. METHODS: This study was registered in PROSPERO (CRD42020160181). A literature search of the PubMed, Embase, Cochrane library and Web of Science databases was performed to retrieve original studies until April of 2022. Twenty-seven studies, including a total of 5462 patients with renal cell carcinoma, were reviewed. Standard meta-analysis methods were used to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio and its 95% confidence interval were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Stata 11.0. Then we verify the meta-analysis resort to bioinformatics (TCGA). RESULTS: Our initial search resulted in 908 articles in total. From PubMed, Embase, Web of Science electronic and Cochrane library databases, 493, 318 and 97 potentially relevant articles were discovered, respectively. We took the analysis between CA9 and disease-specific survival (HR = 1.18, 95% CI: 0.82–1.70, I(2) = 79.3%, P<0.05), a subgroup then was performed to enhance the result (HR = 1.63, 95%CI: 1.30–2.03, I(2) = 26.3%, P = 0.228); overall survival was also parallel with the former (HR = 1.13, 95%CI: 0.82–1.56, I(2) = 79.8%, P<0.05), then a subgroup also be performed (HR = 0.90, 95%CI:0.75–1.07, I(2) = 23.1%, P = 0.246) to verify the result; the analysis between CAIX and progression-free survival got the similar result (HR = 1.73, 95%CI:0.97–3.09, I(2) = 82.4%, P<0.05), we also verify the result by subgroup analysis (HR = 1.04, 95%CI:0.79–1.36, I(2) = 0.0%, P = 0.465); at last the relationship between CAIX and recurrence-free survival got the same result, too (HR = 0.99, 95%CI: 0.95–1.02, I(2) = 57.8%, P = 0.050), the subgroup’s result was also parallel with the former (HR = 1.01, 95%CI: 0.91–1.03, I(2) = 0.00%, P = 0.704). To validate our meta-analysis, we took a bioinformatic analysis based on TCGA database, survival curve between low and high CAIX expression in four endpoints (DSS, OS, PFI, DFI) have corresponding P value (DSS:P = 0.23, OS:P = 0.77, PFI:P = 0.25, DFI:P = 0.78). CONCLUSIONS: CAIX expression in patients with RCC is an exception to predict tumor survival. Both low CAIX expression and high expression are not associated with survivals in RCC patients.