Cheng-Yi Lin1, Ching-Yih Lin2, I-Wei Chang3, Ming-Jen Sheu1, Chien-Feng Li4, Sung-Wei Lee5, Li-Ching Lin6, Ying-En Lee7, Hong-Lin He8. 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center Tainan, Taiwan. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical CenterTainan, Taiwan; Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and TechnologyTainan, Taiwan. 3. Department of Pathology, E-DA Hospital, I-Shou University Kaohsiung, Taiwan. 4. Department of Pathology, Chi-Mei Medical CenterTainan, Taiwan; National Institute of Cancer Research, National Health Research InstitutesTainan, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and TechnologyTainan, Taiwan; Institute of Clinical Medicine, Kaohsiung Medical UniversityKaohsiung, Taiwan. 5. Department of Radiation Oncology, Chi-Mei Medical Center Liouying, Tainan, Taiwan. 6. Department of Radiation Oncology, Chi-Mei Medical Center Tainan, Taiwan. 7. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. 8. Department of Pathology, E-DA Hospital, I-Shou UniversityKaohsiung, Taiwan; Institute of Biomedical Science, National Sun Yat-sen UniversityKaohsiung, Taiwan.
Abstract
BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. METHODS: The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. RESULTS: Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). CONCLUSION: Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer.
BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. METHODS: The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancerpatients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. RESULTS: Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). CONCLUSION: Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer.
Entities:
Keywords:
Thrombospondin 2 (THBS2); chemoradiotherapy; concurrent chemoradiotherapy (CCRT); rectal cancer
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