Insulin-like growth factor receptor-1 overexpression is associated with poor response of rectal cancers to radiotherapy

World J Gastroenterol. 2014 Nov 21;20(43):16268-74. doi: 10.3748/wjg.v20.i43.16268.


Aim: 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).

Conclusion: IGF-1R expression level may serve as a predictive biomarker for radiosensitivity of rectal cancer before preoperative radiotherapy.

Keywords: Immunohistochemistry; Insulin-like growth factor-1 receptor; Preoperative radiotherapy; Rectal carcinoma; Reverse transcription-polymerase chain reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Carcinoma / chemistry
  • Carcinoma / pathology
  • Carcinoma / radiotherapy*
  • Carcinoma / surgery
  • Female
  • Fibrosis
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Necrosis
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • RNA, Messenger / metabolism
  • Radiation Tolerance
  • Radiotherapy, Adjuvant
  • Radiotherapy, Intensity-Modulated*
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / genetics
  • Receptors, Somatomedin / metabolism*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Treatment Outcome
  • Up-Regulation


  • Biomarkers, Tumor
  • IGF1R protein, human
  • RNA, Messenger
  • Receptors, Somatomedin
  • Receptor, IGF Type 1