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含同源结构域基因C10的泛癌分析及其在肺腺癌中的致癌作用

Pan-cancer analysis of homeodomain-containing gene C10 and its carcinogenesis in lung adenocarcinoma.

作者信息

Tan Xiangyuan, Li Zhanzhan, Xie Huayan, Chen Jiarong, Xiao Jian, Zhi Yaofeng, Mo Haixin, Huang Yanming, Liu Aibin

机构信息

Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou 510000, Heyuan, China.

出版信息

Aging (Albany NY). 2023 Dec 27;15(24):15243-15266. doi: 10.18632/aging.205348.

Abstract

We found elevated homeodomain-containing gene C10 (HOXC10) showed dual roles in cancers' prognosis. Some signal pathways associated with tumor were totally positively enriched in HOXC10 for whole cancers. On the contrary, Notch signaling, Wnt-beta catenin signaling, myogenesis, and Hedgehog signaling were almost negatively enriched in HOXC10. Some pathways showed dual roles such as Kras signaling, interferon gram and alpha response, IL6/JAK/STAT3, IL2/STAT5 signaling. HOXC10 was associated with tumor mutation burden and microsatellite instability. HOXC10 also was associated with tumor microenvironment and immune status. HOXC10 was negatively associated with immune score in most cancers except colon adenocarcinoma. The correlations of HOXC10 with immune-related genes presented dual roles in different cancers. Results from our clinical samples indicated that HOXC10 was an independent predictor for distant metastasis-free survival in lung adenocarcinoma (LUAD). Notably, the high levels of HOXC10 were positively correlated with the expression of angiogenic markers, vascular endothelial growth factor and microvessel density, and the number of CTC clusters. Our results demonstrated that aberrant expression happened in most cancers, which also affected the clinical prognosis and involved in progression via multiple signal pathways cancers. HOXC10 overexpression plays an important role in the aggression and metastasis in LUAD, which indicated a potential therapeutic target and an independent factor for the prognosis for LUAD patients.

摘要

我们发现含同源结构域基因C10(HOXC10)在癌症预后中具有双重作用。对于所有癌症而言,一些与肿瘤相关的信号通路在HOXC10中完全呈正富集。相反,Notch信号通路、Wnt-β连环蛋白信号通路、肌生成和Hedgehog信号通路在HOXC10中几乎呈负富集。一些通路呈现双重作用,如Kras信号通路、干扰素γ和α反应、IL6/JAK/STAT3、IL2/STAT5信号通路。HOXC10与肿瘤突变负荷和微卫星不稳定性相关。HOXC10还与肿瘤微环境和免疫状态相关。除结肠腺癌外,HOXC10在大多数癌症中与免疫评分呈负相关。HOXC10与免疫相关基因的相关性在不同癌症中呈现双重作用。我们临床样本的结果表明,HOXC10是肺腺癌(LUAD)无远处转移生存期的独立预测因子。值得注意的是,高水平的HOXC10与血管生成标志物、血管内皮生长因子和微血管密度的表达以及循环肿瘤细胞簇的数量呈正相关。我们的结果表明,HOXC10在大多数癌症中存在异常表达,这也影响了临床预后,并通过多种信号通路参与癌症进展。HOXC10过表达在LUAD的侵袭和转移中起重要作用,这表明它是LUAD患者预后的潜在治疗靶点和独立因素。

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