Expression profile and prognostic significance of HOXB13 in rectal cancer

D. Gao, Yu-Shen Yang, Zhun Wang, Xue-feng Zhao
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Abstract

Background This study aimed to investigate the expression pattern and prognostic significance of HOXB13 in rectal cancer. Methods HOXB13 expression in rectal cancer and normal adjacent tissues was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, and its clinicopathological characteristics and prognosis were statistically tested. Furthermore, we evaluated the association between tumor immune infiltrating cells and HOXB13 using the tumor immune estimation resource (TIMER) database. The potential biological mechanism associated with HOXB13 overexpression was investigated by gene set enrichment analysis (GSEA). Results The expression of HOXB13 messenger RNA and protein in human rectal cancer tissues were significantly higher than those in the normal adjacent tissues (P < 0.05). HOXB13 expression was significantly correlated with depth of invasion, lymphatic invasion, lymph node metastasis, distant metastasis, and pathological tumor node metastasis stage (P < 0.05). Kaplan–Meier survival curves confirmed that HOXB13 overexpression was correlated negatively with overall survival and disease-free survival in rectal cancer (P < 0.05). Also, multivariate Cox regression analysis demonstrated that HOXB13 expression, age, and lymphatic invasion were independent prognostic factors in rectal cancer (P < 0.05). Plus, the results from the TIMER database indicated that HOXB13 expression has a significant association with several immune cell infiltrates. Finally, the GSEA results indicated that HOXB13 participated in the various immune-associated processes, including natural killer cell-mediated cytotoxicity and the T-cell receptor signaling pathway. Conclusion Our study showed an essential role of HOXB13 in rectal cancer immunity and prognosis. Significantly, the overexpression of HOXB13 leads to the worse prognosis for patients with rectal cancer, which will contribute to understanding molecular mechanisms associated with tumor pathogenesis and prognosis in this disease.
HOXB13在直肠癌中的表达谱及预后意义
背景本研究旨在探讨HOXB13在直肠癌中的表达规律及预后意义。方法采用逆转录聚合酶链反应和免疫组化方法检测HOXB13在直肠癌及正常癌旁组织中的表达,并对其临床病理特征及预后进行统计学分析。此外,我们利用肿瘤免疫估计资源(TIMER)数据库评估了肿瘤免疫浸润细胞与HOXB13之间的关系。通过基因集富集分析(GSEA)研究了HOXB13过表达的潜在生物学机制。结果人直肠癌组织中HOXB13信使RNA及蛋白的表达明显高于正常癌旁组织(P < 0.05)。HOXB13表达与浸润深度、淋巴浸润、淋巴结转移、远处转移及病理性肿瘤淋巴结转移分期相关(P < 0.05)。Kaplan-Meier生存曲线证实HOXB13过表达与直肠癌总生存率和无病生存率呈负相关(P < 0.05)。多因素Cox回归分析显示,HOXB13表达、年龄、淋巴浸润是直肠癌预后的独立影响因素(P < 0.05)。此外,来自TIMER数据库的结果表明HOXB13的表达与几种免疫细胞浸润有显著关联。最后,GSEA结果表明HOXB13参与了多种免疫相关过程,包括自然杀伤细胞介导的细胞毒性和t细胞受体信号通路。结论HOXB13在直肠癌免疫和预后中起重要作用。值得注意的是,HOXB13的过表达导致直肠癌患者预后较差,这将有助于了解该疾病肿瘤发病和预后的相关分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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