切换至 "中华医学电子期刊资源库"

中华临床医师杂志(电子版) ›› 2022, Vol. 16 ›› Issue (04) : 337 -342. doi: 10.3877/cma.j.issn.1674-0785.2022.04.009

临床研究

缺氧诱导因子HIF-1α与自噬相关因子Beclin-1和P62在结直肠腺瘤与腺癌癌变中的表达
盛超1,(), 方海明2, 刘璐璐1, 韦瑞玲1   
  1. 1. 230022 合肥,合肥市第三人民医院 安徽医科大学合肥第三临床学院消化内科
    2. 230601 合肥,安徽医科大学第二附属医院消化内科
  • 收稿日期:2021-07-07 出版日期:2022-04-15
  • 通信作者: 盛超

Expression of hypoxia-inducible factor-1α and autophagy related factors Beclin-1 and P62 in colorectal adenoma canceration

Chao Sheng1,(), Haiming Fang2, Lulu Liu1, Ruiling Wei1   

  1. 1. Department of Gastroenterology, the Third People's Hospital of Hefei, Hefei Third Clinical College, Anhui Medical University, Hefei 230022, China
    2. Department of Gastroenterology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
  • Received:2021-07-07 Published:2022-04-15
  • Corresponding author: Chao Sheng
引用本文:

盛超, 方海明, 刘璐璐, 韦瑞玲. 缺氧诱导因子HIF-1α与自噬相关因子Beclin-1和P62在结直肠腺瘤与腺癌癌变中的表达[J/OL]. 中华临床医师杂志(电子版), 2022, 16(04): 337-342.

Chao Sheng, Haiming Fang, Lulu Liu, Ruiling Wei. Expression of hypoxia-inducible factor-1α and autophagy related factors Beclin-1 and P62 in colorectal adenoma canceration[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(04): 337-342.

目的

探索缺氧诱导因子(HIF-1α)与自噬相关因子(Beclin-1)和(P62)在结直肠息肉、结直肠癌(CRC)中表达及与临床病理特征之间的关系。

方法

收集2018年1月至2021年1月合肥市第三人民医院结直肠息肉(包括非腺瘤性和腺瘤性息肉)、结直肠癌患者资料和肠镜标本组织,另取正常患者结直肠粘膜作为对照组。苏木精-伊红(HE)染色并根据肠组织进行病理分型,免疫组织化学方法检测HIF-1α和Beclin-1、P62在息肉、癌组织以及正常肠黏膜表达情况并结合其临床病理资料进行统计分析。共51例患者,男性25例,女性26例,中位年龄58.7±13.9(28~95)岁。其中,腺瘤性息肉14例、非腺瘤性息肉16例、CRC11例及正常结直肠黏膜10例。

结果

HIF-1α在正常结直肠黏膜、非腺瘤性息肉、腺瘤性息肉以及CRC中阳性表达率分别为20.0%、31.2%、64.3%和81.8%;Beclin-1在对应各组阳性率为40.0%、62.5%、85.7%和90.9%;P62在对应各组阳性率为30.0%、56.3%、78.6%和90.9%。与正常组比较,非腺瘤性息肉中HIF-1α、Beclin-1和P62表达差异无统计学意义(P>0.05),但腺瘤性息肉以及CRC中表达差异具有统计意义,呈递增趋势,CRC中表达显著高于腺瘤性息肉和非腺瘤性息肉(P<0.05)。

结论

HIF‐1α以及自噬相关因子Beclin-1和P62在CRC以及腺瘤性息肉表达显著高于非腺瘤性息肉以及正常结直肠黏膜,呈递增趋势,提示缺氧和自噬功能异常可能参与结直肠腺瘤癌变过程。

Objective

To explore the expression of hypoxia-inductive factor (HIF)-1α and autophagy related factors Beclin-1 and P62 in colorectal polyps and cancer.

Methods

Patients with colorectal polyps (include non-adenomatous polyps and adenomatous polyps) or cancer treated at the Third People's Hospital of Hefei from January 2018 to December 2021 were enrolled, and their clinical data and colorectal tissues were collected. Normal colorectal mucosal samples were included as a control group. The expressions of HIF-1α, Beclin-1, and P62 in polyps, carcinoma, and normal intestinal mucosa were detected by immunohistochemical method, and statistical analysis was performed.

Results

A total of 51 patients were enrolled, including 25 males and 26 females. The mean age was 58.7±13.9 (28~95) years old. There were 14 cases of adenomatous polyps, 16 cases of non-adenomatous polyps, 11 cases of CRC, and 10 cases of normal colorectal mucosa. The positive expression rates of HIF-1α in normal colorectal mucosa, non-adenomatous polyps, adenomatous polyps, and CRC were 20.0%, 31.2%, 64.3%, and 81.8%, respectively; the corresponding rates of Beclin-1 were 40.0%, 62.5%, 85.7%, and 90.9%, and those of P62 were 30.0%, 56.3%, 78.6%, and 90.9%. The expression of HIF-1α, Beclin-1, and P62 in non-adenomatous polyps showed no significant difference compared with that of the normal group, while the expression of HIF-1 α, Beclin-1, and P62 in adenomatous polyps and CRC showed a significant difference compared with that of the normal group. Their expression in CRC was significantly higher than that in adenomatous polyps and non-adenomatous polyps (P<0.05).

Conclusion

The expression of HIF-1α and autophagy related factors Beclin-1 and P62 in is significantly higher in adenomatous polyps and CRC than in non-adenomatous polyps and normal colorectal mucosa, and in CRC than in adenomatous polyps, suggesting that hypoxia and autophagy dysfunction may be involved in the carcinogenesis of colorectal adenoma

图1 HIF-1α在CRC、腺瘤性息肉、非腺瘤性息肉以及正常结直肠粘膜中表达。图a为正常组;图b为非腺瘤性息肉;图c为腺瘤性息肉;图d为结直肠癌 注:HIF-1α为缺氧诱导因子-1α;CRC为结直肠癌
图2 Beclin-1在CRC、腺瘤性息肉、非腺瘤性息肉以及正常结直肠粘膜中表达。图a为正常组;图b为非腺瘤性息肉;图c为腺瘤性息肉;图d为结直肠癌 注:Beclin-1为自噬相关蛋白;CRC为结直肠癌
图3 P62在CRC、腺瘤性息肉、非腺瘤性息肉以及正常结直肠粘膜中表达。图a为正常组;图b为非腺瘤性息肉;图c为腺瘤性息肉;图d为结直肠癌 注:P62为自噬底物蛋白;CRC为结直肠癌
图4 各组HIF-1α、Beclin-1、P62表达评分 注:HIF-1α为缺氧诱导因子-1α;Beclin-1为自噬相关蛋白;P62为自噬底物蛋白;Normal为正常结直肠;Non-Ade为非腺瘤性息肉;Ade为腺瘤性息肉;CRC为结直肠癌
1
Kanth P, Grimmett J, Champine M, et al. Hereditary colorectal polyposis and cancer syndromes: a primer on diagnosis and management [J]. Am J Gastroenterol, 2017, 112(10): 1509-1525.
2
Montminy EM, Jang A, Conner M, et al. Screening for colorectal cancer [J]. Med Clin North Am, 2020, 104(6): 1023-1036.
3
Boardman LA, Vilar E, You YN, et al. AGA Clinical practice update on young adult-onset colorectal cancer diagnosis and management: expert review [J]. Clin Gastroenterol Hepatol, 2020, 18(11): 2415-2424.
4
Samec M, Liskova A, Koklesova L, et al. Flavonoids targeting HIF-1: implications on cancer metabolism [J]. Cancers (Basel), 2021, 13(1): 130.
5
齐君君, 韩学锋, 蔡晓岚, 等. 自噬相关基因Beclin1及P62在鼻息肉组织中的表达及临床意义 [J]. 中华耳鼻喉头颈外科杂志, 2016, 51(6): 428-432.
6
Lukmanto D, Khanh VC, Shirota S, et al. Dynamic changes of mouse embryonic stem cell-derived neural stem cells under in vitro prolonged culture and hypoxic conditions [J]. Stem Cells Dev. 2019, 28(21): 1434-1450.
7
Zhang W, Yuan W, Song J, et al. LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α [J]. Biochimie, 2018, 144: 21-27.
8
Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer [J]. Mol Cancer, 2020, 22, 19(1): 12.
9
Qureshi-Baig K, Kuhn D, Viry E, et al. Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway [J]. Autophagy, 2020, 16(8): 1436-1452.
10
Mokarram P, Albokashy M, Zarghooni M, et al. New frontiers in the treatment of colorectal cancer: autophagy and the unfolded protein response as promising targets [J]. Autophagy, 2017, 13(5): 781-819.
11
Kim SY, Song X, Zhang L, et al. Role of Bcl-xL/Beclin-1 in interplay between apoptosis and autophagy in oxaliplatin and bortezomib-induced cell death [J]. Biochem Pharmacol, 2014, 88(2): 178-188.
12
Zhang J, Yang S, Xu B, et al. P62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor [J]. Cell Prolif, 2019, 52(3): e12585.
[1] 钟雅雯, 王煜, 王海臻, 黄莉萍. 肌苷通过抑制线粒体通透性转换孔开放缓解缺氧/复氧诱导的人绒毛膜滋养层细胞凋亡[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 525-533.
[2] 李争光, 宰爽嘉, 吴火峰, 孙华, 张永博, 陈浏阳, 戴睿, 张亮. 昼夜节律相关因子在椎间盘退行性变发病机制中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(05): 457-461.
[3] 杨建波, 马欢, 黄小梅, 刘华柱. 结肠镜辅助下EMR、CSP和RFA术治疗直径<1cm结直肠息肉的疗效和安全性比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 76-79.
[4] 陈樽, 王平, 金华, 周美玲, 李青青, 黄永刚. 肌肉减少症预测结直肠癌术后切口疝发生的应用研究[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(06): 639-644.
[5] 张露平, 黄春玉, 张生澎, 李晶华, 冯力民. 阴道内镜在妊娠期宫颈息肉治疗中的临床应用[J/OL]. 中华腔镜外科杂志(电子版), 2024, 17(05): 301-305.
[6] 王秋生. 胆道良性疾病诊疗策略[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 779-782.
[7] 韩加刚, 王振军. 梗阻性左半结肠癌的治疗策略[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 450-458.
[8] 赵泽云, 李建男, 王旻. 中性粒细胞胞外诱捕网在结直肠癌中的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 524-528.
[9] 王国强, 张纲, 唐建坡, 张玉国, 杨永江. LINC00839 调节miR-17-5p/WEE1 轴对结直肠癌细胞增殖、凋亡和迁移的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 491-499.
[10] 孙晗, 于冰, 武侠, 周熙朗. 基于循环肿瘤DNA 甲基化的结直肠癌筛查预测模型的构建与验证[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 500-506.
[11] 陈倩倩, 袁晨, 刘基, 尹婷婷. 多层螺旋CT 参数、癌胚抗原、错配修复基因及病理指标对结直肠癌预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 507-511.
[12] 丁富贵, 吴泽涛, 董卫国. 家族性腺瘤性息肉病临床特征及生物信息学分析[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 512-518.
[13] 史清泉, 苗彬, 王烁, 陶琳, 沈晨. miR-181a-5p 靶向ATG5 抑制雨蛙素诱导的大鼠胰腺腺泡细胞AR42J自噬的机制研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 524-530.
[14] 杭丽, 张耀辉, 孙文恺. 参菝抗瘤液对结直肠腺瘤性息肉术后肠道功能、炎症指标及复发情况的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 413-416.
[15] 王湛, 李文坤, 杨奕, 徐芳, 周敏思, 苏珈仪, 王亚丹, 吴静. 炎症指标在早发性结直肠肿瘤中的应用[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 802-810.
阅读次数
全文


摘要