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.

Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and literature review

“…After removal of duplication and screening of titles and abstracts, 20 articles were potential eligible for our meta-analysis. After careful reading, 15 studies fulfilled our inclusion criterias [ 16 – 30 ]. Among the included articles, 12 studies [ 16 – 21 , 25 – 30 ] had available data to analyze OS and 5 studies [ 16 , 21 , 22 , 25 , 30 ] had available data to analyze RFS.…”

“…After careful reading, 15 studies fulfilled our inclusion criterias [ 16 – 30 ]. Among the included articles, 12 studies [ 16 – 21 , 25 – 30 ] had available data to analyze OS and 5 studies [ 16 , 21 , 22 , 25 , 30 ] had available data to analyze RFS. In terms of cancer type, 9 studies [ 16 – 24 ] contained or included data of SATB1 expression in CRC patients, 4 studies [ 25 – 28 ] with data on SATB1 expression in GC patients, 2 studies with SATB1 expression in other types of gastrointestinal cancer, more specifically in esophageal cancer [ 29 ] and pancreatic cancer [ 30 ].…”

“…2. Heterogeneity between studies included: Sohaily found that the association between loss of SATB1expression and poor OS was even stronger in right colon cancer patients, which implied that although colorectal cancer is usually considered as a single disease, differences still exist between right-sided, left-sided, sigmoid and rectal cancer both in clinical and biological aspects, however in Sun et al [ 16 ] and Meng et al [ 24 ], they only included rectal cancer patients. Differences in proportion of CRC location might also contribute to the discrepancies; 3.…”

Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients: A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses

“…Indeed, the target prediction by TargetScan, a superior program with the best performance in comparison, also identified AEG-1 and SATB1 as putative targets for miR-888 in the present study. Our previous studies had identified the role of SATB1 and AEG-1 in the progression of rectal cancer, as well as the involvement of the nuclear factor κB signaling pathway for AEG-1 and potential interaction in response to radiation through different canonical pathways for SATB1 by Western blotting and qRT-PCR analysis ( 40 , 42 , 46 ). Thus, these findings are consistent with the results of our present study, which points to an oncogenic role for miR-888 in rectal cancer by modulating targets such as AEG-1 and SATB1.…”

“…These factors were studied on the sections of the blocks (fixation described above) from the same patients at our laboratory. The data for p73 ( n = 74) ( 32 ), p130 ( n = 71) ( 34 ), phosphatase of regenerating liver-3 (PRL-3, n = 73) ( 35 ), endosialin (TEM1, n = 75) ( 36 ), survivin ( n = 47) ( 37 ), peroxisome proliferator-activated receptor δ (PPAR-δ, n = 67) ( 38 ), WRAP53 ( n = 67) ( 39 ), astrocyte elevated gene-1 (AEG-1) ( n = 70) ( 40 ), COX-2 ( n = 77) ( 41 ), and special AT-rich sequence binding protein 1 (SATB1, n = 68) ( 42 ) of primary rectal cancers determined by immunohistochemistry were taken from previous studies conducted with the same cases used in the present study at our laboratory. Apoptosis ( n = 71) was detected by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling) assay ( 43 ).…”