Pathak S.,Linköping University |
Ding Z.-Y.,Cancer Center and State Key Laboratory of Biotherapy |
Adell G.,County Council of Ostergotland |
Holmlund B.,County Council of Ostergotland |
And 3 more authors.
Cancer Biology and Therapy | Year: 2015
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. © 2015 Taylor & Francis Group, LLC.
PubMed | Institute of Digestive Surgery
Type: Journal Article | Journal: Experimental and therapeutic medicine | Year: 2012
The aim of this study was to investigate the relationship between the expression of activating transcription factor 5 (ATF5) and clinicopathological features in human rectal cancer. Relative quantitative real-time RT-PCR and immunohistochemical staining were used to detect ATF5 mRNA and protein expression in 92 paired samples of rectal cancer and distant normal tissues. Immunohistochemical staining of the matched rectal tissue samples revealed that the positive expression rate of the ATF5 protein in rectal cancer was significantly higher compared to that in the normal tissue. Furthermore, the expression of ATF5 in poorly differentiated cancers was higher compared to that in well to moderately differentiated cancers (P=0.013). However, there was no significant association between ATF5 protein expression and patient age, gender, histological tumor type, cell differentiation, invasive depth, lymph node metastasis or distant metastasis (P>0.05). However, to our surprise, there was no difference in the relative mRNA expression levels of ATF5 between normal tissues and rectal cancers. Our findings indicate that overexpression of ATF5 protein may be an important biomarker of the degree of malignancy, and increased expression may be related to the post-transcriptional regulation of ATF5 in rectal cancer tissues.