HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation.
HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation.
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DOI：
10.1016/j.heliyon.2023.e23500
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发表时间：
2024-01-15
期刊：
影响因子：
4
通讯作者：
Sun, Minli
中科院分区：
文献类型：
--
作者：
Weng, Meilin;Lai, Yuling;Ge, Xiaodong;Gu, Wenchao;Zhang, Xixue;Li, Lihong;Sun, Minli
HOXC6在实体瘤的发生中起着重要作用，但其在结直肠癌(CRC)患者免疫环境中的功能相关性仍不确定。我们打算利用癌症基因组图谱数据库(n=1619)，研究HOXC6表达对结直肠癌患者预后的预测价值及其与免疫环境的相关性。验证在来自中山医院(n=200)和上海肿瘤中心(n=300)的队列中进行。免疫组织化学(IHC)染色比较HOXC6高表达组和低表达组肿瘤组织中免疫细胞的表达水平。结直肠癌组织中HOXC6表达水平升高与恶性进展和预后不良有关。HOXC6作为结直肠癌患者生存的危险因素已被证实。受试者工作特性分析证实了其诊断价值，并建立了可靠的预后诺模图。KEGG分析和GSEA分析表明，HOXC6参与了免疫调节，其表达与浸润性免疫细胞的丰度密切相关。在两个队列中诊断为结直肠癌的患者中，HOXC6表达上调，且HOXC6水平高与预后不良相关。HOXC6高表达组Treg细胞、CD68+巨噬细胞、CD66b+中性粒细胞和CD8+T细胞浸润增加，PD-L1和PD-1水平升高，颗粒酶B和穿孔素水平降低。这些发现表明，结直肠癌患者中HOXC6的丰度决定了不良的预后，促进了免疫逃避环境，并指导了CD8+T细胞功能障碍。HOXC6有望成为判断结直肠癌预后的生物标志物。
HOXC6 plays an essential part of the carcinogenesis of solid tumors, but its functional relevance within the immune contexture in patients with colorectal cancer (CRC) is still uncertain. We intended to investigate the predictive value of HOXC6 expression for survival outcomes and its correlation with immune contexture in CRC patients by utilizing the Cancer Genome Atlas database (n = 619). Validation was performed in cohorts from Zhongshan Hospital (n = 200) and Shanghai Cancer Center (n = 300). Immunohistochemical (IHC) staining was utilized to compare the levels of immunocytes infiltrating the tumor between the groups with high and low expression of HOXC6. Elevated levels of HOXC6 expression in CRC tissues were linked to malignant progression and poor prognosis. HOXC6 as a risk factor for survival of CRC patients was confirmed. Receiver operating characteristic analysis confirmed its diagnostic value, and a reliable prognostic nomogram was constructed. KEGG analysis and GSEA showed that HOXC6 participated in immune regulation, and its expression was tightly linked to the abundance of infiltrating immunocytes. HOXC6 was upregulated in patients diagnosed with CRC within the two cohorts, and high HOXC6 levels were correlated with a worse prognosis. The high-HOXC6 expression group showed increased infiltration of Treg cells, CD68+ macrophages, CD66b+ neutrophils, and CD8+ T-cells and elevated levels of PD-L1 and PD-1, but decreased levels of granzyme B and perforin. These findings suggest that HOXC6 abundance in patients with CRC determines a poor prognosis, promotes an immunoevasive environment, and directs CD8+ T-cell dysfunction. HOXC6 is expected to become a prospective biomarker for the outcome of CRC.
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