Status of integrin subunit alpha 4 promoter DNA methylation in colorectal cancer and other malignant tumors: a systematic review and meta-analysis

Background and purpose: Although many recent studies have analyzed the validation of integrin subunit alpha 4 (ITGA4) biomarker for cancer detection in patients with various malignancies, the diagnostic value of ITGA4 methylation for malignant tumors remains uncertain. We performed a systematic review and metaanalysis to unravel the relationship between ITGA4 promoter methylation status and malignant tumors. Experimental approach: A meta-analysis was performed using the metaphor package in R 3.5 and Meta- Disc 1.4 software. Data were derived from a search of main electronic databases up to January 2022. SROC analysis was used to evaluate the status of ITGA4 promoter methylation in colorectal cancer (CRC) and other cancers. A total of 1232 tumor samples and 649 non-tumor samples from 13 studies were analyzed. Findings/Results: The pooled results including all types of cancer provided evidence that ITGA4 hypermethylation was more frequent in tumor samples than non-tumor samples (OR 13.32, 95% CI 7.96- 22.29). Methylation of ITGA4 has a pooled sensitivity of 0.95 (95% CI: 0.94-0.97), a pooled specificity of 0.57 (95% CI: 0.54-0.60), and an area under the curve (AUC) of 0.94. When the analysis was performed independently for CRC, it revealed a higher association (OR = 20.77, 95% CI: 9.15-47.15). The assessment of ITGA4 methylation of tissue samples resulted in a pooled sensitivity of 0.99 (95% CI: 0.97-1.00) and a pooled specificity of 0.90 (95% CI: 0.86-0.93), and AUC of 0.94 for the diagnosis of CRC. Conclusion and implications: ITGA4 methylation analysis is a reliable method for CRC screening in tissue samples.