title: Low thrombospondin 2 expression is predictive of low tumor regression after neoadjuvant chemoradiotherapy in rectal cancer.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center Tainan, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Ching-Yih
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University Kaohsiung, Taiwan.
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center Tainan, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Sheu
authors.affiliation: 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.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Chi-Mei Medical Center Liouying, Tainan, Taiwan.
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Chi-Mei Medical Center Tainan, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Ying-En
authors.initials: YE
authors.lastname: Lee
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou UniversityKaohsiung, Taiwan; Institute of Biomedical Science, National Sun Yat-sen UniversityKaohsiung, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: He
keywords: Thrombospondin 2 (THBS2); chemoradiotherapy; concurrent chemoradiotherapy (CCRT); rectal cancer