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.

中文翻译：

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H2.0样同源盒在结直肠癌发生发展中的潜在双重作用及其预后价值

背景。H2.0 样同源盒( HLX ) 在多种造血系统恶性肿瘤中高度表达。然而， HLX在结直肠癌（CRC）患者发生和进展中的作用却鲜有报道。方法。在这项研究中，数据是从癌症基因组图谱和基因表达综合数据库收集的。通过R包“pROC”分析HLX的诊断价值。使用“survival”和“survminer”包估计总体生存率。建立列线图来预测 CRC 患者的 1 年、3 年和 5 年总生存率。采用CIBERSORT软件计算22种免疫细胞的相对比例。结果。CRC 患者中HLX表达下调。值得注意的是，HLX表达随着CRC分期（I期~III期）而增加，HLX高表达的CRC患者预后较差。与癌旁样本相比，CRC 样本中HLX启动子甲基化水平显着升高。我们还发现这6个miRNA靶向HLX基因，导致其下调，并且在CRC和正常样本中HLX表达与其下游靶基因BRI3BP呈负相关。最后，我们发现HLX高表达组和低HLX表达组之间的12种免疫浸润细胞存在显着差异。HLX与8个免疫检查点（PD-1（PDCD1）、CTLA4、PDL-1（CD274）、PDL-2（PDCD1LG2）、CD80、CD86、LAG3和TIGIT）表达呈显着正相关。结论。HLX可能在结直肠癌早期发挥抑癌作用，但在晚期表现出促癌作用。同时，HLX可以作为CRC的可靠预后指标。