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浙江大学学报(医学版)  2020, Vol. 49 Issue (6): 725-731    DOI: 10.3785/j.issn.1008-9292.2020.12.07
原著     
大肠癌患者肿瘤相关血管中胰岛素受体表达及其与肿瘤组织病理学特征的关系
杨泽然1,*(),张欣1,马杰1,金丽1,何徐军2
1. 浙江省人民医院 杭州医学院附属人民医院病理科, 浙江 杭州 310014
2. 浙江省人民医院临床医学研究所, 浙江 杭州 310014
Expression of tumor-associated vascular insulin receptor in colorectal cancer and its relationship with tumor pathological features
YANG Zeran1,*(),ZHANG Xin1,MA Jie1,JIN Li1,HE Xujun2
1. Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China
2. Institute of Clinical Medicine, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
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摘要:

目的: 研究肿瘤相关血管中胰岛素受体(IR)在伴或不伴代谢综合征(MS)大肠癌患者中的表达及其与大肠癌病理特征之间的关系。方法: 采用组织芯片结合免疫组织化学技术检测220例根治性切除大肠癌患者肿瘤相关血管中IR表达,分析在伴和不伴MS两类患者肿瘤相关血管中IR表达与大肠癌病理学特征(病理学亚型、组织学分级、浸润深度、淋巴结转移和TNM分期)之间的关系。结果: IR在正常大肠组织血管内皮细胞中呈阴性表达,而在大肠癌组织及其与正常交界区血管内皮细胞中呈阳性表达。伴MS患者肿瘤相关血管中IR高表达检出率低于不伴MS的患者(分别为21.6%和41.0%,P < 0.05)。肿瘤相关血管中IR高表达与肿瘤深部浸润、淋巴结转移、高TNM分期相关(P < 0.05或P < 0.01),肿瘤相关血管中IR高表达可增加肿瘤深部浸润风险(OR=2.21,95% CI:1.10~4.44,P < 0.05)、淋巴结转移风险(OR=2.21,95% CI:1.26~3.86,P < 0.01)和高TNM分期风险(OR=2.08,95% CI:1.19~3.63,P < 0.05)。上述相关性可存在于不伴MS患者中,在伴MS的患者中未体现。结论: 血管内皮细胞IR高表达与肿瘤浸润、转移等侵袭性特征相关,可作为大肠癌患者,特别是不伴MS大肠癌患者预后判断的潜在指标。

关键词: 大肠癌胰岛素受体肿瘤相关血管代谢综合征病理学    
Abstract:

Objective: To study the expression of tumor associated vascular insulin receptor (TVIR) in colorectal cancer with or without metabolic syndrome (MS) and its relationship with the pathological features of colorectal cancer. Methods: The expression of TVIR in 220 colorectal cancer specimens was detected by tissue microarray and immunohistochemistry. The relationships between the expression of TVIR and the pathological features (pathological subtypes, histological grade, invasion depth, lymph node metastasis and TNM stage) of colorectal cancer with/without MS were analyzed. Results: The insulin receptor expression was observed in colorectal cancer tissue or border area between cancer and normal tissue, but not in normal intestinal tissue. The high-expression rates of TVIR in MS group was remarkably lower than that of non-MS group (21.6%vs. 41.0%, P < 0.05). TVIR high expression was significantly associated with tumor deep invasion, lymph node metastasis and high TNM stage (P < 0.05 or P < 0.01). Univariate logistic regression analysis showed high-expression of TVIR to be significantly associated with risk of deep invasion (OR=2.21, 95% CI: 1.10-4.44, P < 0.05), lymph node metastasis (OR=2.21, 95% CI: 1.26-3.86, P < 0.01) and high TNM stage (OR=2.08, 95% CI: 1.19-3.63, P < 0.05). Such associations can be observed in patients without MS, but not in patients with MS. Conclusions: High-expression of TVIR is associated with aggressive pathological features such as invasion, lymph node metastasis and high TNM stage of colorectal cancer, especially for those patients without MS. TVIR could be a useful biological marker for prognosis of colorectal cancer.

Key words: Colorectal carcinoma    Insulin receptor    Tumor-associated vessel    Metabolic syndrome    Pathology
收稿日期: 2020-04-08 出版日期: 2021-01-14
CLC:  R735.3+4  
基金资助: 浙江省自然科学基金(LY18H160044);浙江省医药卫生科技计划(2019KY024)
通讯作者: 杨泽然     E-mail: yangzeran_66@163.com
作者简介: 杨泽然(1966-), 男, 博士, 副主任医师, 副教授, 主要从事肿瘤病理和血管新生机制研究; E-mail:yangzeran_66@163.com; https://orcid.org/0000-0003-0615-0256
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引用本文:

杨泽然,张欣,马杰,金丽,何徐军. 大肠癌患者肿瘤相关血管中胰岛素受体表达及其与肿瘤组织病理学特征的关系[J]. 浙江大学学报(医学版), 2020, 49(6): 725-731.

YANG Zeran,ZHANG Xin,MA Jie,JIN Li,HE Xujun. Expression of tumor-associated vascular insulin receptor in colorectal cancer and its relationship with tumor pathological features. J Zhejiang Univ (Med Sci), 2020, 49(6): 725-731.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.12.07        http://www.zjujournals.com/med/CN/Y2020/V49/I6/725

图 1  胰岛素受体(IR)在正常大肠组织和肿瘤相关血管中的表达
图 2  胰岛素受体(IR)在大肠癌患者肿瘤相关血管中的表达(免疫组织化学染色)
组别 n 年龄 女性 代谢综合征 体重指数≥25 kg/m2* 高血压 空腹血糖≥6.1 mmol/L或糖尿病 血三酰甘油≥1.7 mmol/L 低高密度脂蛋白
“—”无相关数据.*22例(IR低表达10例,IR高表达12例)患者缺少体质量和(或)身高记录.
IR低表达 137 63±12 57(41.6) 29(21.2) 25(19.7) 71(51.8) 46(33.6) 26(19.0) 44(32.1)
IR高表达 83 62±14 33(39.8) 8(9.6) 12(16.9) 32(38.6) 16(19.3) 14(16.9) 27(32.5)
t/χ2 0.458 0.073 5.252 0.235 3.679 5.412 0.156 0.004
P >0.05 >0.05 <0.05 >0.05 >0.05 <0.05 >0.05 >0.05
表 1  大肠癌患者肿瘤相关血管中胰岛素受体(IR)表达与代谢综合征及其组分的关系
组织病理学特征 不伴代谢综合征 P 伴代谢综合征 P 合计 P
IR低表达 IR高表达 IR低表达 IR高表达 IR低表达 IR高表达
*仅对非黏液腺癌患者进行组织学分级.
病理亚型
  非黏液腺癌 102(94.4) 72(96.0) >0.05 26(89.7) 8(100.0) >0.05 128(93.4) 80(96.4) >0.05
  黏液癌 6(5.6) 3(4.0) 3(10.3) 0(0.0) 9(6.6) 3(3.6)
组织学分级*
  低级别 92(90.2) 59(81.9) >0.05 21(80.8) 4(50.0) >0.05 113(88.3) 63(78.8) >0.05
  高级别 10(9.8) 13(18.1) 5(19.2) 4(50.0) 15(11.7) 17(21.2)
深部浸润 74(68.5) 62(82.7) <0.05 23(89.7) 8(100.0) >0.05 97(70.8) 70(84.3) <0.05
淋巴结转移 41(38.0) 47(62.7) <0.01 18(62.1) 5(62.5) >0.05 59(43.1) 52(62.7) <0.01
高TNM分期 43(39.8) 47(62.7) <0.01 18(62.1) 5(62.5) >0.05 61(44.5) 52(62.7) <0.01
表 2  肿瘤相关血管中胰岛素受体(IR)表达与伴或不伴代谢综合征大肠癌患者病理特征之间的关系
病理特征 不伴代谢综合征患者 所有患者
OR(95%CI) P OR(95%CI) P
高级别 2.02(0.83~4.91) >0.05 2.05(0.95~4.38) >0.05
深部浸润 2.16(1.05~4.46) <0.05 2.21(1.10~4.44) <0.05
淋巴结转移 2.72(1.48~5.00) <0.01 2.21(1.26~3.86) <0.01
高TNM分期 2.52(1.37~4.63) <0.01 2.08(1.19~3.63) <0.05
表 3  肿瘤相关血管中胰岛素受体(IR)高表达与大肠癌组织病理学特征之间关系的Logistic回归分析结果
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