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已发表论文
识别趋化因子系统相关表型以预测泛癌免疫特征及肺腺癌预后标志物
Authors Zhao T, Wu X, Guo S, Nie J, Fang S, Wang L, Li X, Nie T, Yao K , Du X, Wang Y, Yuan Y, Ni J
Received 18 May 2025
Accepted for publication 4 September 2025
Published 22 September 2025 Volume 2025:18 Pages 13213—13234
DOI https://doi.org/10.2147/JIR.S537256
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Junhao Wang
Tianming Zhao,1– 4,* Xu Wu,1,2,* Shiqi Guo,5,* Jun Nie,5 Shitao Fang,5 Liangchao Wang,6 Xiaojuan Li,1,2 Tingting Nie,1,2 Kecheng Yao,7 Xinge Du,1,2 Yingnan Wang,1,2 Yurong Yuan,8 Jixiang Ni6
1Department of Respiratory and Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 3Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, People’s Republic of China; 4Clinical Medical Research Center for Precision Diagnosis and Treatment of Lung Cancer and Management of Advanced Cancer Pain of Hubei Province, Yichang, Hubei, People’s Republic of China; 5Department of Cardiothoracic Surgery, The First College of Clinical Medical of Science, Yichang Central People’s Hospital, China Three Gorges University, Yichang, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 7Department of Geriatrics, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People’s Republic of China; 8Yichang Emergency Medical Center, Yichang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yurong Yuan, Email 474810935@qq.com Jixiang Ni, Email jxnee77@163.com
Background: The chemokine system modulates tumor cell characteristics and influences immune cell function. This research investigates the roles of chemokines and their receptors (CaCRs) across multiple cancers and establishes a reliable CaCRs-based prognostic model for lung adenocarcinoma (LUAD).
Methods: Gene expression data were sourced from the UCSC-Xena platform and the GEO database. The chemokine score was calculated using the ssGSEA algorithm. A CaCRs-based prognostic signature was constructed and validated for LUAD. Expression levels of signature genes in lung cancer tissues were verified.
Results: Dysregulation of CaCRs expression was observed in multiple cancers. The chemokine score has shown prognostic features in various tumors. In the LUAD cohort, a seven-gene signature of CaCRs (CCR2, CCR4, CCR6, XCR1, CCL20, CXCL17, and XCL2) was constructed as a prognostic model, identifying a poorer prognosis for high-risk groups. mRNA levels of CCR2, CCR4, CCR6, and XCR1 were significantly reduced in lung cancer tissues compared to adjacent normal tissues, while CCL20 was markedly overexpressed in tumor tissues. Furthermore, CCL20 promoted A549 cell proliferation via the MAPK pathway, with JNK inhibitors effectively blocking CCL20-induced proliferation.
Conclusion: This study highlights the substantial role of CaCRs in immunity and prognosis. The identified seven-gene signature of CaCRs provides a new prognostic tool for LUAD.
Keywords: chemokine, chemokine receptor, prognosis, pan-cancer, LUAD
1Department of Respiratory and Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 3Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, People’s Republic of China; 4Clinical Medical Research Center for Precision Diagnosis and Treatment of Lung Cancer and Management of Advanced Cancer Pain of Hubei Province, Yichang, Hubei, People’s Republic of China; 5Department of Cardiothoracic Surgery, The First College of Clinical Medical of Science, Yichang Central People’s Hospital, China Three Gorges University, Yichang, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 7Department of Geriatrics, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People’s Republic of China; 8Yichang Emergency Medical Center, Yichang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yurong Yuan, Email 474810935@qq.com Jixiang Ni, Email jxnee77@163.com
Background: The chemokine system modulates tumor cell characteristics and influences immune cell function. This research investigates the roles of chemokines and their receptors (CaCRs) across multiple cancers and establishes a reliable CaCRs-based prognostic model for lung adenocarcinoma (LUAD).
Methods: Gene expression data were sourced from the UCSC-Xena platform and the GEO database. The chemokine score was calculated using the ssGSEA algorithm. A CaCRs-based prognostic signature was constructed and validated for LUAD. Expression levels of signature genes in lung cancer tissues were verified.
Results: Dysregulation of CaCRs expression was observed in multiple cancers. The chemokine score has shown prognostic features in various tumors. In the LUAD cohort, a seven-gene signature of CaCRs (CCR2, CCR4, CCR6, XCR1, CCL20, CXCL17, and XCL2) was constructed as a prognostic model, identifying a poorer prognosis for high-risk groups. mRNA levels of CCR2, CCR4, CCR6, and XCR1 were significantly reduced in lung cancer tissues compared to adjacent normal tissues, while CCL20 was markedly overexpressed in tumor tissues. Furthermore, CCL20 promoted A549 cell proliferation via the MAPK pathway, with JNK inhibitors effectively blocking CCL20-induced proliferation.
Conclusion: This study highlights the substantial role of CaCRs in immunity and prognosis. The identified seven-gene signature of CaCRs provides a new prognostic tool for LUAD.
Keywords: chemokine, chemokine receptor, prognosis, pan-cancer, LUAD