Quantified CIN Score From Cell-free DNA as a Novel Noninvasive Predictor of Survival in Patients With Spinal Metastasis

Frontiers in Cell and Developmental Biology - Tập 9
Chen Su1, Minglei Yang1, Nanzhe Zhong1, Dong Yu2, Jian Jiao1, Dongjie Jiang1, Yasong Xiao1, Wei Wei1, Tianzhen Wang3, Yan Lou1, Zhenhua Zhou1, Wei Xu1, Wan Wan1, Zhipeng Wu1, Haifeng Wei1, Tielong Liu1, Jian Zhao1, Xinghai Yang1, Jianru Xiao1
1Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
2Center of Translational Medicine, Naval Medical University, Shanghai, China
3Weizmann Institute of Sciences, Rehovot, Israel

Tóm tắt

Purpose: Most currently available scores for survival prediction of patients with bone metastasis lack accuracy. In this study, we present a novel quantified CIN (Chromosome Instability) score modeled from cfDNA copy number variation (CNV) for survival prediction.Experimental Design: Plasma samples collected from 67 patients with bone metastases from 11 different cancer types between November 2015 and May 2016 were sent through low-coverage whole genome sequencing followed by CIN computation to make a correlation analysis between the CIN score and survival prognosis. The results were validated in an independent cohort of 213 patients.Results: During the median follow-up period of 598 (95% CI 364–832) days until December 25, 2018, 124 (44.3%) of the total 280 patients died. Analysis of the discovery dataset showed that CIN score = 12 was the optimal CIN cutoff. Validation dataset showed that CIN was elevated (score ≥12) in 87 (40.8%) patients, including 5 (5.75%) with head and neck cancer, 11 (12.6%) with liver and gallbladder cancer, 11 (12.6%) with cancer from unidentified sites, 21 (24.1%) with lung cancer, 7 (8.05%) with breast cancer, 4 (4.60%) with thyroid cancer, 6 (6.90%) with colorectal cancer, 4 (4.60%) with kidney cancer, 2 (2.30%) with prostate cancer, and 16 (18.4%) with other types of cancer. Further analysis showed that patients with elevated CIN were associated with worse survival (p < 0.001). For patients with low Tokuhashi score (≤8) who had predictive survival of less than 6 months, the CIN score was able to distinguish patients with a median overall survival (OS) of 443 days (95% CI 301–585) from those with a median OS of 258 days (95% CI 184–332).Conclusion: CNV examination in bone metastatic cancer from cfDNA is superior to the traditional predictive model in that it provides a noninvasive and objective method of monitoring the survival of patients with spine metastasis.

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Tài liệu tham khảo

Ahmed, 2018, Predicting Survival for Metastatic Spine Disease: a Comparison of Nine Scoring Systems, Spine J., 18, 1804, 10.1016/j.spinee.2018.03.011

Ay, 2012, High D-Dimer Levels Are Associated with Poor Prognosis in Cancer Patients, HAEMATOLOGICA, 97, 1158, 10.3324/haematol.2011.054718

Bartels, 2008, Spinal Extradural Metastasis: Review of Current Treatment Options, CA: A Cancer J. Clinicians, 58, 245, 10.3322/ca.2007.0016

Batista, 2016, Emerging and Established Clinical, Histopathological and Molecular Parametric Prognostic Factors for Metastatic Spine Disease Secondary to Lung Cancer: Helping Surgeons Make Decisions, J. Clin. Neurosci., 34, 15, 10.1016/j.jocn.2016.05.023

Bauer, 2002, Surgical Strategy for Spinal Metastases, Spine (Phila Pa 1976), 27, 1124, 10.1097/00007632-200205150-00027

Bianchi, 2015, Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies, JAMA, 314, 162, 10.1001/jama.2015.7120

Collado Martín, 2014, Clinical Guideline SEOM: Cancer of Unknown Primary Site, CLIN. TRANSL ONCOL., 16, 1091, 10.1007/s12094-014-1244-0

Dharajiya, 2018, Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing, CLIN. CHEM., 64, 329, 10.1373/clinchem.2017.277517

Ellinger, 2011, The Role of Cell-free Circulating DNA in the Diagnosis and Prognosis of Prostate Cancer, Urol. Oncol. Semin. Original Invest., 29, 124, 10.1016/j.urolonc.2009.05.010

Gronroos, 2018, Tolerance of Chromosomal Instability in Cancer: Mechanisms and Therapeutic Opportunities, CANCER RES., 78, 6529, 10.1158/0008-5472.can-18-1958

Jansson, 2006, Survival, Complications and Outcome in 282 Patients Operated for Neurological Deficit Due to Thoracic or Lumbar Spinal Metastases, EUR. SPINE J., 15, 196, 10.1007/s00586-004-0870-6

Ji, 2019, Identifying Occult Maternal Malignancies from 1.93 Million Pregnant Women Undergoing Noninvasive Prenatal Screening Tests, GENET. MED., 21, 2293, 10.1038/s41436-019-0510-5

Kawahara, 2009, Total en bloc spondylectomy for spinal tumors: surgical techniques and related basic background, Orthop. Clin. North America, 40, 47, 10.1016/j.ocl.2008.09.004

Li, 2018, Combined Fibrinogen and Neutrophil–Lymphocyte Ratio as a Predictive Factor in Resectable Colorectal Adenocarcinoma, Cmar, 10, 6285, 10.2147/cmar.s161094

Mayrhofer, 2018, Cell-free DNA Profiling of Metastatic Prostate Cancer Reveals Microsatellite Instability, Structural Rearrangements and Clonal Hematopoiesis, GENOME MED., 10, 85, 10.1186/s13073-018-0595-5

Mehra, 2018, Plasma Cell-free DNA Concentration and Outcomes from Taxane Therapy in Metastatic Castration-Resistant Prostate Cancer from Two Phase III Trials (FIRSTANA and PROSELICA), Eur. Urol., 74, 283, 10.1016/j.eururo.2018.02.013

Mo, 2020, Genome-wide Chromosomal Instability by Cell-free DNA Sequencing Predicts Survival in Patients with Metastatic Breast Cancer, The Breast, 53, 111, 10.1016/j.breast.2020.07.004

Oellerich, 2017, Using Circulating Cell-free DNA to Monitor Personalized Cancer Therapy, Crit. Rev. Clin. Lab. Sci., 54, 205, 10.1080/10408363.2017.1299683

Pelegrini de Almeida, 2018, Reliability of Tokuhashi Score to Predict Prognosis: Comparison of 117 Patients, World Neurosurg., 111, e1, 10.1016/j.wneu.2017.11.033

Sioutos, 1995, Spinal Metastases from Solid Tumors. Analysis of Factors Affecting Survival, Cancer, 76, 1453, 10.1002/1097-0142(19951015)76:8<1453:aid-cncr2820760824>3.0.co;2-t

Stover, 2018, Association of Cell-free DNA Tumor Fraction and Somatic Copy Number Alterations with Survival in Metastatic Triple-Negative Breast Cancer, Jco, 36, 543, 10.1200/jco.2017.76.0033

Sutcliffe, 2013, A Systematic Review of Evidence on Malignant Spinal Metastases: Natural History and Technologies for Identifying Patients at High Risk of Vertebral Fracture and Spinal Cord Compression, Health Technol. Assess., 17, 1, 10.3310/hta17420

Tan, 2016, Evaluation of Scoring Systems and Prognostic Factors in Patients with Spinal Metastases from Lung Cancer, Spine (Phila Pa 1976), 41, 638, 10.1097/BRS.0000000000001279

Tan, 2019, Environmental Stresses Induce Karyotypic Instability in Colorectal Cancer Cells, MBoC, 30, 42, 10.1091/mbc.e18-10-0626

Tang, 2015, Metastatic Spinal Cord Compression from Non-small-cell Lung Cancer Treated with Surgery and Adjuvant Therapies, The J. Bone Jt. Surgery-American Volume, 97, 1418, 10.2106/jbjs.n.01124

Tang, 2016, Effect of Surgery on Quality of Life of Patients with Spinal Metastasis from Non-small-cell Lung Cancer, J. Bone Jt. Surg., 98, 396, 10.2106/jbjs.o.00629

Tokuhashi, 2005, A Revised Scoring System for Preoperative Evaluation of Metastatic Spine Tumor Prognosis, Spine (Phila Pa 1976), 30, 2186, 10.1097/01.brs.0000180401.06919.a5

Tokuhashi, 1990, Scoring System for the Preoperative Evaluation of Metastatic Spine Tumor Prognosis, Spine (Phila Pa 1976), 15, 1110, 10.1097/00007632-199011010-00005

Tomita, 2001, Surgical Strategy for Spinal Metastases, Spine (Phila Pa 1976), 26, 298, 10.1097/00007632-200102010-00016

Tran, 2021, Using Cell-free DNA for HCC Surveillance and Prognosis, JHEP Rep., 3, 100304, 10.1016/j.jhepr.2021.100304

van der Linden, 2005, Prediction of Survival in Patients with Metastases in the Spinal Column, Cancer, 103, 320, 10.1002/cncr.20756

Vanderstichele, 2017, Chromosomal Instability in Cell-free DNA as a Highly Specific Biomarker for Detection of Ovarian Cancer in Women with Adnexal Masses, CLIN. CANCER RES., 23, 2223, 10.1158/1078-0432.ccr-16-1078

Varadhachary, 2014, Cancer of Unknown Primary Site, N. Engl. J. Med., 371, 757, 10.1056/NEJMra1303917

Yang, 2019, Development and Validation of a Novel Survival Prediction Model in Patients with Spinal Metastasis from Non-small Cell Lung Cancer, Spine (Phila Pa 1976), 44, 246, 10.1097/BRS.0000000000002816

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Frontiers in Cell and Developmental Biology

Tập 9

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