Differential impact of CX3CL1 on lung cancer prognosis in smokers and non-smokers
Ying-Chieh Su
Department of Thoracic Surgery, Chi Mei Medical Center, Tainan, Taiwan (R.O.C)
Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan (R.O.C)
Search for more papers by this authorHan Chang
Department of Pathology, China Medical University Hospital, Taichung, Taiwan (R.O.C)
Search for more papers by this authorShih-Jung Sun
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorCheng-Yi Liao
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorLing-Yi Wang
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorJiunn-Lang Ko
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorCorresponding Author
Jinghua T. Chang
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan (R.O.C)
Correspondence
Jinghua T. Chang, PhD, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C).
Email: [email protected]
Search for more papers by this authorYing-Chieh Su
Department of Thoracic Surgery, Chi Mei Medical Center, Tainan, Taiwan (R.O.C)
Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan (R.O.C)
Search for more papers by this authorHan Chang
Department of Pathology, China Medical University Hospital, Taichung, Taiwan (R.O.C)
Search for more papers by this authorShih-Jung Sun
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorCheng-Yi Liao
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorLing-Yi Wang
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorJiunn-Lang Ko
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Search for more papers by this authorCorresponding Author
Jinghua T. Chang
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C)
Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan (R.O.C)
Correspondence
Jinghua T. Chang, PhD, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (R.O.C).
Email: [email protected]
Search for more papers by this authorAbstract
CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms, which mediates different biological activities. Recent studies have revealed the potential of CX3CL1 signaling pathway as a target for the treatment of inflammation and cancer. The correlation between expression of CX3CL1 and prognosis of patients varies among cancers. In this study, based on CX3CL1 immunohistochemistry in non-small cell lung cancer, CX3CL1 levels were positively associated with cancer stage (Pearson chi-square, P = 0.048) and lymph node status (P = 0.033). Interestingly, survival effects of CX3CL1 were only observed in patients with smoking history and adenocarcinoma (AD, log rank, P = 0.027), but not in patients with squamous cell carcinoma (SQ). The median survival time of patients with smoking history and low level CX3CL1 expressing AD was 1538 days, while that of patients with smoking history and high level CX3CL1 expressing AD was 396 days. Cox regression models showed adverse effects of high CX3CL1 levels only in AD patients with smoking history (hazard ratio = 3.01, p = 0.034), but not in AD patients without smoking history or in SQ patients with smoking history. The results of this study suggest that CX3CL1 plays different roles in lung tumorigenesis in smokers and non-smokers, and different CX3CL1-based therapeutic strategies are needed depending on patient smoking status and tumor type. Furthermore, high level of CX3CL1 expression enhances nodal metastasis by activating JNK & MMP2/MMP9 activity in lung cancer cells.
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.
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