title: Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer.
abstract: Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasn't been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.
authors.affiliation: a Department of Gastrointestinal Surgery ; West China Hospital; Sichuan University ; Chengdu , China.|b Department of Oncology and Department of Clinical and Experimental Medicine ; Linköping University ; Linköping , Sweden.
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Meng
authors.affiliation: b Department of Oncology and Department of Clinical and Experimental Medicine ; Linköping University ; Linköping , Sweden.
authors.forename: Surajit
authors.initials: S
authors.lastname: Pathak
authors.affiliation: c Cancer Center and State Key Laboratory of Biotherapy; West China Hospital; Sichuan University ; Chengdu , China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Ding
authors.affiliation: d School of Medicine; Örebro University ; Örebro , Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: e Department of Oncology ; County Council of Östergötland ; Linköping , Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Adell
authors.affiliation: e Department of Oncology ; County Council of Östergötland ; Linköping , Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Holmlund
authors.affiliation: f Institute of Digestive Surgery; State Key Laboratory of Biotherapy and Cancer Center; West China Hospital; Sichuan University ; Chengdu , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Gastrointestinal Surgery ; West China Hospital; Sichuan University ; Chengdu , China.|f Institute of Digestive Surgery; State Key Laboratory of Biotherapy and Cancer Center; West China Hospital; Sichuan University ; Chengdu , China.
authors.forename: Zong-Guang
authors.initials: ZG
authors.lastname: Zhou
authors.affiliation: b Department of Oncology and Department of Clinical and Experimental Medicine ; Linköping University ; Linköping , Sweden.|f Institute of Digestive Surgery; State Key Laboratory of Biotherapy and Cancer Center; West China Hospital; Sichuan University ; Chengdu , China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
mesh_terms: D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D063868:Patient Outcome Assessment; D011379:Prognosis; D011836:Radiation Tolerance / Q000235:genetics; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human
keywords: Ingenuity Pathway Analysis; SATB1; colorectal cancer; preoperative radiotherapy; prognosis