| Institution: | 1. Crown Princess Victoria Children''s Hospital, Division of Pediatrics, Linköping University Hospital, Linköping, Sweden;2. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;3. Department of Immunology, University Hospital Zurich, Zurich, Switzerland;4. Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden;5. Laboratory of Molecular Medicine, Department of Clinical Immunology Section 7631, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;1. Department of Surgery, School of Medicine, Keio University, Tokyo, Japan;2. Department of Radiology, School of Medicine, Keio University, Tokyo, Japan;3. Division of Diagnostic Pathology, School of Medicine, Keio University, Tokyo, Japan;1. Department of Dermatology, Mayo Clinic, Rochester, Minnesota;2. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota;3. Division of Hematology, Mayo Clinic, Rochester, Minnesota;1. Department of Respiratory Medicine, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;2. Department of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100000, China;3. Department of Endocrinology, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;4. Department of Rheumatology, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;2. Division of Thoracic and Foregut Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa |
| Abstract: | Melanoma is a highly aggressive cancer with a poor prognosis. We found that immune response played important roles in melanoma metastasis by GSEA analysis. Therefore, we constructed the immune risk score (IRS) by the LASSO-COX analysis in the sequencing metastatic samples from the TCGA database. Then, initial diagnosis patients with metastasis were selected as the test cohort. Importantly, we adopted overall survival (OS) as the survival outcome for initial diagnosis patients, while adopting the observed survival interval (OBS) as the survival outcome for sequencing samples which could avoid biologically meaningless associations. We found that the IRS had high power for predicting 2, 3 and 5-year survival in training (AUC = 0.70, 0.69 and 0.68) and test cohorts (AUC = 0.72, 0.70 and 0.65). The IRS was significantly associated with prognosis both in the metastatic samples (HR = 1.60, 95% CI = 1.16–2.19) and patients with metastasis (HR = 2.89, 95% CI = 1.69–4.53). we further used other independent melanoma cohorts from the GEO databases to confirm the reliability and validity of the IRS (P < 0.01 in all cohorts). The practical nomogram was also built using the IRS and clinical information with high c-index both in training (0.76, 95%CI = 0.72–0.80) and test cohorts (0.72, 95%CI = 0.65–0.79). Finally, IRS showed the predictive value of survival outcome and response of immunotherapy patients, and increased the predictive ability of current immune checkpoint gene markers. In conclusion, the IRS can serve as a potential biomarker for prognosis and responsiveness to immune checkpoint blockade immunotherapy in metastatic melanoma patients. |
