title: Insulin-like growth factor receptor-1 overexpression is associated with poor response of rectal cancers to radiotherapy.
abstract: OBJECTIVE
  To explore the potential correlation between insulin-like growth factor receptor-1 (IGF-1R) expression and rectal cancer radiosensitivity.
  
  
  METHODS
  Eighty-seven rectal cancer patients (cTNM I-III) treated in our department between January 2011 and December 2012 were enrolled. All subjects were treated with preoperative radiotherapy and radical resection of rectal carcinoma. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to detect IGF-1R expression in pre-treatment and postoperative colorectal cancer specimens. Radiosensitivity for rectal cancer specimens was evaluated by observing rectal carcinoma mass regression combined with fibrosis on HE staining, degree of necrosis and quantity of remaining tumor cells. The relative IGF-1R expression was evaluated for association with tumor radiosensitivity.
  
  
  RESULTS
  Immunohistochemistry showed diffuse IGF-1R staining on rectal cancer cells with various degrees of signal density. IGF-1R expression was significantly correlated with cTNM staging (P = 0.012) while no significant association was observed with age, sex, tumor size and degree of differentiation (P = 0.424, 0.969, 0.604, 0.642). According to the Rectal Cancer Regression Grades (RCRG), there were 31 cases of RCRG1 (radiation sensitive), 28 cases of RCRG2 and 28 cases of RCRG3 (radiation resistance) in 87 rectal cancer subjects. IGF-1R protein hyper-expression was significantly correlated with a poor response to radiotherapy (P < 0.001, r = 0.401). RT-PCR results from pre-radiation biopsy specimens also showed that IGF-1R mRNA negative group exhibited a higher radiation sensitivity (P < 0.001, r = 0.497). Compared with the pre-radiation biopsy specimens, the paired post-operative specimens showed a significantly increased IGF-1R protein and mRNA expression in the residual cancer cells (P < 0.001, respectively).
  
  
  CONCLUSIONS
  IGF-1R expression level may serve as a predictive biomarker for radiosensitivity of rectal cancer before preoperative radiotherapy.
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Wu
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Qin-Hong
authors.initials: QH
authors.lastname: Cao
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Che
authors.initials: C
authors.lastname: Chen
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Wei-Su
authors.initials: WS
authors.lastname: Li
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Fu-Kun
authors.initials: FK
authors.lastname: Liu
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Xue-Quan
authors.initials: XQ
authors.lastname: Yao
authors.affiliation: Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D018714:Radiotherapy, Adjuvant; D050397:Radiotherapy, Intensity-Modulated; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1
keywords: Immunohistochemistry; Insulin-like growth factor-1 receptor; Preoperative radiotherapy; Rectal carcinoma; Reverse transcription-polymerase chain reaction