The Potential Dual Role of H2.0-like Homeobox in the Tumorgenesis and Development of Colorectal Cancer and Its Prognostic Value.

Background: H2.0-like homeobox (HLX) is highly expressed in several hematopoietic malignancies. However, the role of HLX in the carcinogenesis and progression of colorectal cancer (CRC) patients has rarely been reported.

Methods: In this study, the data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. The diagnostic value of HLX was analyzed by the R package "pROC." The overall survival was estimated using the "survival" and "survminer" packages. A nomogram was established to predict 1-, 3-, and 5-year overall survival of CRC patients. The CIBERSORT software was employed to calculate the relative proportions of 22 immune cells.

Results: HLX expression was downregulated in CRC patients. Remarkably, HLX expression was increased with stage (stage I-stage III) of CRC, and the CRC patients with high HLX expression exhibited a poor prognosis. The promoter methylation level of HLX was prominently increased in CRC samples compared to paracancerous samples. We also found that the six miRNAs target HLX genes, leading to its downregulation, and HLX expression had a negative correlation with its downstream target gene BRI3BP in both CRC and normal samples. Finally, we found that the 12 immune infiltrating cells were observably different between high and low HLX expression groups. The HLX had a significant positive correlation with 8 immune checkpoints (PD-1 (PDCD1), CTLA4, PDL-1 (CD274), PDL-2 (PDCD1LG2), CD80, CD86, LAG3, and TIGIT) expressions.

Conclusion: HLX probably played a carcinostasis role in the early stages of CRC but exhibited a cancer-promoting effect in the advanced stages. Meanwhile, HLX could serve as a reliable prognostic indicator for CRC.