Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis

Bing Lu; Jiawen Shi; Tong Cheng; Congshuo Wang; Manyu Xu; Pingping Sun; Xiaojing Zhang; Lei Yang; Peng Li; Han Wu; Xiaoling Kuai

doi:10.3389/fphar.2024.1397656

Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis

Front Pharmacol. 2024 Jun 3:15:1397656. doi: 10.3389/fphar.2024.1397656. eCollection 2024.

Authors

Bing Lu^#¹, Jiawen Shi^#^{1

2}, Tong Cheng^{1

3}, Congshuo Wang⁴, Manyu Xu^{1

3}, Pingping Sun¹, Xiaojing Zhang¹, Lei Yang¹, Peng Li⁵, Han Wu⁵, Xiaoling Kuai⁴

Affiliations

¹ Department of Clinical Biobank, Nantong University Affiliated Hospital, Nantong, China.
² Department of Pathology and Pathophysiology, School of Medicine, Nantong University, Nantong, China.
³ Department of Oncology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
⁴ Department of Gastroenterology, Nantong University Affiliated Hospital, Nantong, Jiangsu, China.
⁵ Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu, China.

^# Contributed equally.

Abstract

Objective: Gastric cancer (GC) is the world's third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration.

Methods: We assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration (p < 0.05).

Results: We found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren's type cells, T cells (CD4⁺ and CD8⁺), and CD68⁺ macrophages in the TME. Kaplan-Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor.

Conclusion: Our study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

Keywords: CCL14; chemokine drug target; immune checkpoint; immunotherapy; tumor microenvironment; tumor-infiltrating immune cells.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Nos 81874067 , 82073025, 82072778) and Jiangsu Province Capability Improvement Project through Science, Technology and Education (Grant No. ZDXK202234).