Department of General Surgery, 194043Dalian University Affiliated Xinhua Hospital, Dalian 116021, China.
Int J Biol Markers. 2022 Jun;37(2):140-148. doi: 10.1177/17246008221076151. Epub 2022 Mar 16.
This study aimed to investigate the expression pattern and prognostic significance of HOXB13 in rectal cancer.
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).
The expression of HOXB13 messenger RNA and protein in human rectal cancer tissues were significantly higher than those in the normal adjacent tissues ( < 0.05). HOXB13 expression was significantly correlated with depth of invasion, lymphatic invasion, lymph node metastasis, distant metastasis, and pathological tumor node metastasis stage ( < 0.05). Kaplan-Meier survival curves confirmed that HOXB13 overexpression was correlated negatively with overall survival and disease-free survival in rectal cancer ( < 0.05). Also, multivariate Cox regression analysis demonstrated that HOXB13 expression, age, and lymphatic invasion were independent prognostic factors in rectal cancer ( < 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.
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.
本研究旨在探讨 HOXB13 在直肠癌中的表达模式及其预后意义。
采用逆转录-聚合酶链反应和免疫组织化学方法检测 HOXB13 在直肠癌及正常相邻组织中的表达，对其临床病理特征和预后进行统计学检验。此外，我们使用肿瘤免疫评估资源（TIMER）数据库评估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）研究与 HOXB13 过表达相关的潜在生物学机制。
HOXB13 信使 RNA 和蛋白在人直肠癌组织中的表达明显高于正常相邻组织（<0.05）。HOXB13 表达与浸润深度、淋巴侵袭、淋巴结转移、远处转移和病理肿瘤淋巴结转移分期显著相关（<0.05）。Kaplan-Meier 生存曲线证实 HOXB13 过表达与直肠癌的总生存和无病生存呈负相关（<0.05）。此外，多变量 Cox 回归分析表明，HOXB13 表达、年龄和淋巴侵袭是直肠癌的独立预后因素（<0.05）。此外，TIMER 数据库的结果表明 HOXB13 表达与几种免疫细胞浸润有显著相关性。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。
本研究表明 HOXB13 在直肠癌免疫和预后中起着重要作用。HOXB13 的过表达导致直肠癌患者预后更差，这将有助于理解与肿瘤发病机制和预后相关的分子机制。
