Upregulated Ubiquitin D is a Favorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy

Abstract

Chia-Lin Chou,1,2 Tzu-Ju Chen,1,3– 5 Wan-Shan Li,1,3,5 Sung-Wei Lee,6 Ching-Chieh Yang,7,8 Yu-Feng Tian,2 Cheng-Yi Lin,9 Hong-Lin He,10 Hung-Chang Wu,8,11 Yow-Ling Shiue,5,12 Chien-Feng Li,12– 14 Yu-Hsuan Kuo5,8,11,12 1Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan; 2Division of Colon and Rectal Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan; 3Department of Pathology, Chi Mei Medical Center, Tainan, 710, Taiwan; 4Department of Clinical Pathology, Chi Mei Medical Center, Tainan, 710, Taiwan; 5Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan; 6Department of Radiation Oncology, Chi Mei Medical Center, Liouying, 736, Taiwan; 7Department of Radiation Oncology, Chi Mei Medical Center, Tainan, 710, Taiwan; 8College of Pharmacy and Science, Chia Nan University, Tainan, Taiwan; 9Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 710, Taiwan; 10Department of Pathology, E-DA Hospital & E-DA Cancer Hospital, I-Shou University, Kaohsiung, 82445, Taiwan; 11Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan; 12Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan; 13Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan; 14National Institute of Cancer Research, National Health Research Institutes, Miaoli County, 35053, TaiwanCorrespondence: Yu-Hsuan Kuo; Chien-Feng Li, No. 901, Zhonghua Road Yongkang Dist, Tainan City, Taiwan, Tel [phone], Fax [phone] ; Fax [phone], Email [email protected]; [email protected]: For locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT.Patients and Methods: We analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival.Results: Upregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004).Conclusion: UBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.Keywords: ubiquitin D, UBD, FAT10, rectal cancer, concurrent chemoradiotherapy

Keywords

• ubiquitin d
• ubd
• fat10
• rectal cancer
• concurrent chemoradiotherapy