Potential prognostic and immunotherapeutic value of calponin 1: A pan-cancer analysis

Hengli Zhou; Junyu Ke; Changhua Liu; Menglu Zhu; Bijuan Xiao; Qi Wang; Rui Hou; Yueer Zheng; Yongqiang Wu; Xingting Zhou; Xinlin Chen; Huafeng Pan

doi:10.3389/fphar.2023.1184250

Potential prognostic and immunotherapeutic value of calponin 1: A pan-cancer analysis

Front Pharmacol. 2023 Apr 21:14:1184250. doi: 10.3389/fphar.2023.1184250. eCollection 2023.

Authors

Hengli Zhou¹, Junyu Ke^{2

3}, Changhua Liu¹, Menglu Zhu¹, Bijuan Xiao¹, Qi Wang¹, Rui Hou⁴, Yueer Zheng⁵, Yongqiang Wu³, Xingting Zhou⁶, Xinlin Chen², Huafeng Pan^{1

7}

Affiliations

¹ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
² School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
³ Gaozhou Hospital of Traditional Chinese Medicine, Gaozhou, China.
⁴ Namyue Natural Medicine Co., Ltd., Macau, Macau SAR, China.
⁵ Yu Fai Co., Ltd., Macau, Macau SAR, China.
⁶ Namyue Group Co., Ltd., Macau, Macau SAR, China.
⁷ Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, China.

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

Keywords: angiogenesis; calponin 1; gastric cancer; immunotherapy; pan-cancer; prognosis.

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant no. 82174319), Key Laboratory of State Administration of Traditional Chinese Medicine (202110071448237400), Key Laboratory of Guangdong Province (2022B1212010012), Guangdong Key R&D Program (grant no. 2020B1111100011), Maoming Science and Technology Special Funds Project (grant no. 220121154550402), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (no. ZYYCXTD-C-202208), and Discipline Collaborative Innovation Team of Guangzhou University of Traditional Chinese Medicine (grant no. 2021xk36).