Zhou Hengli, Ke Junyu, Liu Changhua, Zhu Menglu, Xiao Bijuan, Wang Qi, Hou Rui, Zheng Yueer, Wu Yongqiang, Zhou Xingting, Chen Xinlin, Pan Huafeng
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2023 Apr 21;14:1184250. doi: 10.3389/fphar.2023.1184250. eCollection 2023.
Emerging evidence has suggested a pro-oncogenic role of calponin 1 (CNN1) in the initiation of a variety of cancers. Despite this, CNN1 remains unknown in terms of its effects and mechanisms on angiogenesis, prognosis, and immunology in cancer. The expression of CNN1 was extracted and analyzed using the TIMER, UALCAN, and GEPIA databases. Meanwhile, we analyzed the diagnostic value of CNN1 by using PrognoScan and Kaplan-Meier plots. To elucidate the value of CNN1 in immunotherapy, we used the TIMER 2.0 database, TISIDB database, and Sangerbox database. Gene set enrichment analysis (GSEA) was used to analyze the expression pattern and bio-progression of CNN1 and the vascular endothelium growth factor (VEGF) in cancer. The expressions of CNN1 and VEGF in gastric cancer were confirmed using immunohistochemistry. We used Cox regression analysis to investigate the association between pathological characteristics, clinical prognosis, and CNN1 and VEGF expressions in patients with gastric cancer. CNN1 expression was higher in normal tissues than it was in tumor tissues of most types of cancers. However, the expression level rebounds during the development of tumors. High levels of CNN1 indicate a poor prognosis for 11 tumors, which include stomach adenocarcinoma (STAD). There is a relationship between CNN1 and tumor-infiltrating lymphocytes (TILs), and the marker genes NRP1 and TNFRSF14 of TILs are significantly related to CNN1 expression in gastric cancers. The GSEA results confirmed the lower expression of CNN1 in tumors when compared to normal tissues. However, CNN1 again showed an increasing trend during tumor development. In addition, the results also suggest that CNN1 is involved in angiogenesis. The immunohistochemistry results validated the GSEA result (take gastric cancer as an example). Cox analysis suggested that high CNN1 expression and high VEGF expression are closely associated with poor clinical prognosis. Our study has shown that CNN1 expression is aberrantly elevated in various cancers and positively correlates with angiogenesis and the immune checkpoint, contributing to cancer progression and poor prognosis. These results suggest that CNN1 could serve as a promising candidate for pan-cancer immunotherapy.
新出现的证据表明,钙调蛋白1(CNN1)在多种癌症的发生中具有促癌作用。尽管如此,CNN1在癌症血管生成、预后和免疫学方面的作用及机制仍不清楚。使用TIMER、UALCAN和GEPIA数据库提取并分析CNN1的表达。同时,我们使用PrognoScan和Kaplan-Meier图分析CNN1的诊断价值。为了阐明CNN1在免疫治疗中的价值,我们使用了TIMER 2.0数据库、TISIDB数据库和Sangerbox数据库。基因集富集分析(GSEA)用于分析CNN1和血管内皮生长因子(VEGF)在癌症中的表达模式和生物学进程。使用免疫组织化学法证实了CNN1和VEGF在胃癌中的表达。我们使用Cox回归分析来研究胃癌患者的病理特征、临床预后与CNN1和VEGF表达之间的关联。在大多数类型癌症中,CNN1在正常组织中的表达高于肿瘤组织。然而,在肿瘤发展过程中其表达水平会反弹。高水平的CNN1表明包括胃腺癌(STAD)在内的11种肿瘤预后不良。CNN1与肿瘤浸润淋巴细胞(TILs)之间存在关联,并且TILs的标记基因NRP1和TNFRSF14与胃癌中CNN1的表达显著相关。GSEA结果证实,与正常组织相比,肿瘤中CNN1的表达较低。然而,在肿瘤发展过程中CNN1再次呈现上升趋势。此外,结果还表明CNN1参与血管生成。免疫组织化学结果验证了GSEA结果(以胃癌为例)。Cox分析表明,高CNN1表达和高VEGF表达与不良临床预后密切相关。我们的研究表明,CNN1在各种癌症中的表达异常升高,并且与血管生成和免疫检查点呈正相关,促进癌症进展和预后不良。这些结果表明,CNN1有望成为泛癌免疫治疗的候选靶点。