title: The X-linked inhibitor of apoptosis protein is an independent prognostic marker for rectal adenocarcinoma after preoperative chemoradiotherapy.
abstract: Rectal cancer (RC) is a common malignancy of the gastrointestinal tract. Preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) is considered an effective treatment as it down-stages advanced RC. X-linked inhibitor of apoptosis protein (XIAP) and survivin participate in the regulation of apoptosis, a key process in carcinogenesis and tumor progression. However, the prognostic value of concomitant expression of XIAP and survivin in RC patients undergoing neoadjuvant CCRT is not well established. Expression of XIAP and survivin proteins was evaluated by immunohistochemical staining of pre-CCRT and post-CCRT specimens of 58 rectal cancer patients. Clinicopathological parameters were also analyzed. In pre-CCRT biopsy specimens, high survivin expression was significantly associated with perineural invasion (p = 0.025), metastatic status (p = 0.015), and advanced disease stage (I-IV, p = 0.025; early vs. late, p = 0.047). In post-CCRT surgical specimens, high XIAP expression was significantly associated with age (p = 0.037), T stage (p = 0.025), disease stage (p = 0.019), and tumor regression grade (TRG) (p = 0.000). High survivin expression was significantly correlated with T stage (p = 0.044), N stage (p = 0.028), metastasis (p = 0.007), disease stage (p = 0.001), and TRG (p = 0.033). Pearson correlation calculations showed a positive correlation between XIAP and survivin immunoreactivity (p = 0.000). Patients with low XIAP and low survivin expression tended to have significantly longer overall survival (p = 0.006 and 0.001, respectively). In multivariable Cox regression analysis, patients with high XIAP, perineural invasion, and advanced stage had significantly shorter overall survival (p = 0.000, 0.002 and 0.000, respectively). In conclusion, high expression of XIAP and survivin is associated with advanced stage and poor prognosis. Expression of XIAP is positively correlated with that of survivin. These data suggest that XIAP is an independent prognostic marker and might be considered as therapy target for rectal cancer after neoadjuvant therapy.
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Tsao
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Pei
authors.initials: HP
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.|Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan. cychai@kmu.edu.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cychai@kmu.edu.tw.|Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cychai@kmu.edu.tw.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. cychai@kmu.edu.tw.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
keywords: Concurrent chemoradiotherapy; Rectal cancer; Survivin; X-linked inhibitor of apoptosis protein