title: Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.
abstract: Genes associated with protein folding have been found to have certain prognostic significance in a subset of cancers. The aim of this study is to evaluate the clinical impact of DNAJC12 expression in patients with rectal cancers receiving neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. Through data mining from a public transcriptomic dataset of rectal cancer focusing on genes associated with protein folding, we found that DNAJC12, a member of the HSP40/DNAJ family, was the most significant such gene correlated with the CCRT response. We further evaluated the expression of DNAJC12 by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancers. From this set, we statistically analyzed the association of DNAJC12 expression with various clinicopathological factors, tumor regression grade, overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS). High expression of DNAJC12 was significantly associated with advanced pre- and post-treatment tumor status (P<0.001), advanced pre- and post-treatment nodal status (P<0.001), increased vascular invasion (P=0.015), increased perineural invasion (P=0.023) and lower tumor regression grade (P=0.009). More importantly, high expression of DNAJC12 was found to be correlated with poor prognosis for OS (P=0.0012), DFS (P<0.0001) and LRFS (P=0.0001). In multivariate analysis, DNAJC12 overexpression still emerged as an independent prognosticator for shorter OS (P=0.040), DFS (P<0.001) and LRFS (P=0.016). The data indicate that DNAJC12 overexpression acts as a negative predictive factor for the response to neoadjuvant CCRT and was significantly associated with shorter survival in patients with rectal cancers receiving neoadjuvant CCRT followed by surgery.
authors: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors: Hong-Lin
authors: HL
authors: He
authors: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Ying-En
authors: YE
authors: Lee
authors: Department of Colorectal Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors: Hsin-Pao
authors: HP
authors: Chen
authors: Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.
authors: Chung-Hsi
authors: CH
authors: Hsing
authors: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
authors: I-Wei
authors: IW
authors: Chang
authors: Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors: Yow-Ling
authors: YL
authors: Shiue
authors: Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors: Sung-Wei
authors: SW
authors: Lee
authors: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors: Chao-Tien
authors: CT
authors: Hsu
authors: Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan.
authors: Li-Ching
authors: LC
authors: Lin
authors: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors: Ting-Feng
authors: TF
authors: Wu
authors: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan. Electronic address: angelo.p@yahoo.com.tw.
authors: Chien-Feng
authors: CF
authors: Li
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C484558:DNAJC12 protein, human; D012097:Repressor Proteins
keywords: CCRT; Chemoradiotherapy; DNAJC12; HSP40; Rectal cancer