title: Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer.
abstract: OBJECTIVE
  To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.
  
  
  METHODS
  We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients, including 111 patients with colon cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to stage IV according to the 7(th) edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. All patients underwent resection of primary colorectal tumors. The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining. The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed.
  
  
  RESULTS
  ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors (25.8%). There were 7.4%, 24.1%, 22.2% and 46.3% of patients with ARID1A loss staged at TNM stage I, II, III and IV, respectively, compared with 20.0%, 22.6%, 27.7% and 29.7% of patients without ARID1A loss staged at TNM stage I, II, III and IV, respectively. In patients with ARID1A loss, the distant metastasis rate was 46.3%. However, only 29.7% of patients without ARID1A loss were found to have distant metastasis. In terms of pathologic differentiation, there were 25.9%, 66.7% and 7.4% with poorly, moderately and well differentiated tumors in patients with ARID1A loss, and 14.2%, 72.3% and 13.5% with poorly, moderately and well differentiated tumors in patients without ARID1A loss, respectively. ARID1A loss was associated with late TNM stage (P = 0.020), distant metastasis (P = 0.026), and poor pathological classification (P = 0.035). However, patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stage IV colorectal cancer (HR = 2.49, 95%CI: 1.13-5.51).
  
  
  CONCLUSIONS
  ARID1A protein loss is associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stage IV patients.
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wei
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: De-Shen
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Xi
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Chen
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Zhao-Lei
authors.initials: ZL
authors.lastname: Zeng
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Rui-Yu
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Ya-Xin
authors.initials: YX
authors.lastname: Huang
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Miao-Zhen
authors.initials: MZ
authors.lastname: Qiu
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Luo
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: AT-rich interactive domain 1A; Clinicopathologic characteristics; Colorectal cancer; Prognosis; Switching defective/sucrose non-fermenting complexes