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胰岛素样生长因子受体-1过表达与直肠癌放疗反应不佳相关。

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

作者信息

Wu Xiao-Yu, Wu Zhen-Feng, Cao Qin-Hong, Chen Che, Chen Zhi-Wei, Xu Zhe, Li Wei-Su, Liu Fu-Kun, Yao Xue-Quan, Li Gang

机构信息

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.

出版信息

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

Abstract

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.

摘要

目的

探讨胰岛素样生长因子受体-1(IGF-1R)表达与直肠癌放射敏感性之间的潜在相关性。

方法

选取2011年1月至2012年12月在我科接受治疗的87例直肠癌患者(cTNM I-III期)。所有患者均接受术前放疗及直肠癌根治性切除术。采用免疫组织化学和逆转录聚合酶链反应(RT-PCR)检测治疗前及术后结直肠癌标本中IGF-1R的表达。通过观察直肠癌肿块消退情况并结合HE染色的纤维化程度、坏死程度及残留肿瘤细胞数量,评估直肠癌标本的放射敏感性。评估IGF-1R相对表达与肿瘤放射敏感性的相关性。

结果

免疫组织化学显示,直肠癌细胞上有弥漫性IGF-1R染色,信号密度程度不一。IGF-1R表达与cTNM分期显著相关(P = 0.012),而与年龄、性别、肿瘤大小及分化程度无显著相关性(P = 0.424、0.969、0.604、0.642)。根据直肠癌消退分级(RCRG),87例直肠癌患者中,RCRG1级(放射敏感)31例,RCRG2级28例,RCRG3级(放射抗拒)28例。IGF-1R蛋白高表达与放疗反应差显著相关(P < 0.001,r = 0.401)。放疗前活检标本的RT-PCR结果也显示,IGF-1R mRNA阴性组具有较高的放射敏感性(P < 0.001,r = 0.497)。与放疗前活检标本相比,配对的术后标本显示残留癌细胞中IGF-1R蛋白和mRNA表达显著增加(P均< 0.001)。

结论

IGF-1R表达水平可作为术前放疗前直肠癌放射敏感性的预测生物标志物。

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