[1]姜秋利,鲁华东,郑景妹,等.结直肠癌组织中RREB1 和ANKRD1 的表达与临床病理特征和预后的相关性研究[J].现代检验医学杂志,2023,38(01):16-21.[doi:10.3969/j.issn.1671-7414.2023.01.004]
　JIANG Qiu-li,LU Hua-dong,ZHENG Jing-mei,et al.Correlation between the Expression of RREB1 and ANKRD1 and Clinicopathological Features and Prognosis in Colorectal Cancer[J].Journal of Modern Laboratory Medicine,2023,38(01):16-21.[doi:10.3969/j.issn.1671-7414.2023.01.004]
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结直肠癌组织中RREB1 和ANKRD1 的表达与临床病理特征和预后的相关性研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年01期
页码:
16-21
栏目:
论著
出版日期:
2023-01-15

文章信息/Info

Title:
Correlation between the Expression of RREB1 and ANKRD1 and Clinicopathological Features and Prognosis in Colorectal Cancer
文章编号:
1671-7414（2023）01-016-06
作者:
姜秋利; 鲁华东; 郑景妹; 管瑛瑛
（复旦大学附属中山医院厦门医院病理科，福建厦门 361000）
Author(s):
JIANG Qiu-li;  LU Hua-dong;  ZHENG Jing-mei;  GUAN Ying-ying
(Department of Pathology, Xiamen Branch, Zhongshan Hospital Affiliated of Fudan University, Fujian Xiamen 361000, China)
关键词:
结直肠癌; ras 反应元件结合蛋白1; ankyrin 重复结构域1
分类号:
R735.3；R730.43
DOI:
10.3969/j.issn.1671-7414.2023.01.004
文献标志码:
A
摘要:
目的 探讨结直肠癌（colorectal cancer，CRC）组织ras 反应元件结合蛋白1 (ras-responsive element bindingprotein 1，RREB1)，ankyrin 重复结构域1 (ankyrin repeat domain 1，ANKRD1）的表达及与临床病理特征和预后不良的关系。方法 选取2013 年1 月～ 2016 年12 月复旦大学附属中山医院厦门医院收治的105 例CRC 患者，应用免疫组织化学SP 法检测CRC 患者癌组织和癌旁组织RREB1 和ANKRD1 蛋白表达，分析RREB1 和ANKRD1 蛋白表达与患者临床病理特征的关系，患者均随访5 年，比较不同RREB1 和ANKRD1 表达患者的预后情况，并分析CRC 患者预后不良的影响因素。采用Spearman 相关系数分析RREB1 与ANKRD1 表达的相关性。结果 CRC 癌组织RREB1 蛋白阳性率（59.05%）显著高于癌旁组织(27.61%)，差异有统计学意义（χ2=21.120，P=0.000）。CRC 癌组织ANKRD1 蛋白阳性率(31.43%) 显著低于癌旁组织(60.95%)，差异有统计学意义（χ2=18.410，P=0.000）。TNM 分期Ⅲ期、淋巴结转移N1 ～ N2 患者RREB1 蛋白阳性率高于TNM 分期Ⅰ～Ⅱ期、淋巴结转移N0 患者，差异有统计学意义（χ2=4.263，8.199，均P ＜ 0.05）。TNM 分期Ⅲ期、淋巴结转移N1 ～ N2 患者ANKRD1 蛋白阳性率低于TNM 分期Ⅰ～Ⅱ期、淋巴结转移N0 患者，差异有统计学意义（χ2=5.515，7.411，均P ＜ 0.05）。RREB1 高表达组5 年生存率（54.84%）低于RREB1 低表达组（74.42%），差异有统计学意义（χ2=5.459，P=0.020）；ANKRD1 高表达组的5 年生存率（78.79%）高于ANKRD1 低表达组（55.56%），差异有统计学意义（χ2=5.130，P=0.024）。RREB1 高表达（HR=2.437，95%CI：1.113 ～ 4.684）、ANKRD1 低表达(HR=0.573，95%CI：0.185 ～ 1.952)、TNM 分期Ⅲ期(HR=2.202, 95%CI：1.357 ～ 4.215)和淋巴结转移N1 ～ N2(HR=1.247, 95%CI：1.532 ～ 4.368) 是CRC 患者预后不良的危险因素 (均P ＜ 0.05)。Spearman秩相关分析结果，CRC 癌组织中RREB1 与ANKRD1 表达呈负相关（r=-0.389，P=0.036）。结论 CRC 癌组织中RREB1 表达升高，而 ANKRD1 表达降低，二者共同参与CRC 的发生发展，有望成为评估CRC 患者预后的组织肿瘤标志物。
Abstract:
Objective To investigate the expression of ras response element-binding protein 1 (RREB1) and ankyrin repeat domain 1 (ANKRD1) in colorectal cancer (CRC) tissues and their relationship with clinicopathological features and poor prognosis. Methods A total of 105 CRC patients admitted to Xiamen Branch, Zhongshan Hospital Affiliated of Fudan University from January 2013 to December 2016 were selected and immunohistochemical SP method was used to detect the protein expression of RREB1 and ANKRD1 in CRC cancer tissue and paracancerous tissue. The relationship between RREB1 and ANKRD1 protein expression and clinicopathological characteristics of patients was analyzed. All patients were followed up for 5 years,the prognosis of patients with different RREB1 and ANKRD1 expressions was compared, and the influencing factors of poor prognosis of CRC patients were analyzed.Spearman correlation coefficient was used to analyze the correlation between RREB1 and ANKRD1 expression. Results The positive rate of RREB1 protein in CRC cancer tissues（59.05%）which was significantly higher than in adjacent tissues（27.61%）, and the difference was statistically significant (χ2=21.120, P=0.000).The positive rate of ANKRD1 protein in CRC cancer tissues （31.43%）which was significantly lower than in adjacent tissues（60.95%）, and the difference was statistically significant (χ2=18.410, P=0.000). The positive rate of RREB1 protein in patients with TNM stage III and lymph node metastasis N1 ～ N2 was higher than that in patients with TNM stage I ～ II and lymph node metastasis N0, and the differences were statistically significant (χ2=4.263, 8.199, all P<0.05).The positive rate of ANKRD1 protein in patients with TNM stage III and lymph node metastasis N1 ～ N2 was lower than that in patients with TNM stage I ～ II and lymph node metastasis N0, and the differences were statistically significant (χ2=5.515, 7.411, all P<0.05).The 5-year survival rate of RREB1 high expression group was 54.84%, which was lower than 74.42% of RREB1 low expression group, and the difference was statistically significant (χ2=5.459, P=0.020). The 5-year survival rate of ANKRD1 high expression group was 78.79%, which was higher than 55.56% of ANKRD1 low expression group, and the difference was statistically significant (χ2=5.130, P=0.024).High expression of RREB1 (HR=2.437, 95%CI: 1.113 ～ 4.684), low expression of ANKRD1 (HR=0.573, 95%CI: 0.185 ～ 1.952), TNM stage III (HR=2.202, 95%CI: 1.357 ～ 4.215) ) and lymph node metastasis N1 ～ N2 (HR=1.247, 95%CI: 1.532 ～ 4.368) were risk factors for poor prognosis of CRC patients (all P ＜ 0.05).The results of Spearman rank correlation analysis showed that the expression of RREB1 and ANKRD1 in CRC cancer tissues was negatively correlated (r=-0.389, P=0.036). Conclusion The expression of RREB1 was increased in CRC cancer tissue, while the expression of ANKRD1 was decreased. Both of them were involved in the occurrence and development of CRC, and are expected to become tissue tumor markers for evaluating the prognosis of CRC patients.

参考文献/References:

[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al.Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA-A Cancer Journal for Clinicians,2018, 68(6): 394-424.
[2] 杨婕琳, 陈文婷, 胡晓利. 结直肠癌组织中硫氧还蛋白-1 与硫氧还蛋白互作蛋白的表达及其临床意义[J]. 现代检验医学杂志, 2021, 36（6）：22-26.
YANG Jielin,CHEN Wenting,HU Xiaoli. Expression and clinical significance of thioredoxin-1 and thioredoxin interacting protein in colorectal cancer [ J ] .Journal of Modern Laboratory Medicine,2021,36(6):22-26.
[3] STEFANI C, MIRICESCU D, STANESCU-SPINU I I, et al. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis:Where are we now?[J]. International Journal of Molecular Sciences, 2021, 22(19): 10260.
[4] DENG Yanan, XIA Zijing, ZHANG Peng, et al.Transcription factor RREB1: From target genes towards biological functions[J]. International Journal of Biological Sciences, 2020, 16(8): 1463-1473.
[5] KENT O A, SAHA M, COYA U D E , et al . Haploinsufficiency of RREB1 causes a noonan-like RASopathy via epigenetic reprogramming of RASMAPK pathway genes[J]. Nature Communications,2020, 11(1): 4673.
[6] HUI Bingqing, JI Hao, XU Yetao, et al. RREB1-induced upregulation of the lncRNA AGAP2-AS1 regulates the proliferation and migration of pancreatic cancer partly through suppressing ANKRD1 and ANGPTL4[J]. Cell Death & Disease, 2019, 10(3): 207.
[7] LUO Yongwen, ZHOU Jun, TANG Jianing, et al.MINDY1 promotes bladder cancer progression by stabilizing YAP[J]. Cancer Cell International, 2021,21(1): 395.
[8] TANG Jianning, LUO Yongwen, XIAO Liang. USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ[J]. Cell Death & Disease, 2022, 13(4):326.
[9] 张愉涵, 陈宏达, 卢明, 等. 结直肠癌筛查和早期诊断生物标志物研究进展[J]. 中华流行病学杂志,2021, 42(1): 142-148.
ZHANG Yuhan, CHEN Hongda, LU Ming, et al.Progress in research of biomarkers for colorectal cancer screening and early detection [J]. Chinese Journal of Epidemiology, 2021,42(1):142-148.
[10] 李立方, 仇丽, 胡凯. 锌指蛋白在基因转录翻译及肿瘤发生发展中的调控作用机制研究进展[J]. 山东医药, 2021, 61(30): 83-87.
LI Lifang, QIU Li, HU Kai. Research progress on the regulatory mechanism of Zinc finger protein in gene transcription and translation and tumorigenesis and development[J]. Shandong Medical Journal, 2021,61(30): 83-87.
[11] YAO Juanjuan, ZHONG Liang, ZHONG Pengqiang, et al. RAS-responsive element-binding protein 1 blocks the granulocytic differentiation of myeloid leukemia cells[J]. Oncology Research, 2019, 27(7): 809-818.
[12] GAO Qi, WU Yunhua, LU Chaoxiang, et al.Knockdown of RREB1 inhibits cell proliferation via enhanced p16 expression in gastric cancer[J]. Cell Cycle (Georgetown, Tex.), 2021, 20(23): 2465-2475.
[13] SU Jie, MORGANI S M, DAVID C J , et al. TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1[J]. Nature, 2020, 577(7791):566-571.
[14] WANG Lijun, LI Jing, WANG Rongli, et al. NGF signaling interacts with the hippo/YAP pathway to regulate cervical cancer progression[J]. Frontiers in Oncology, 2021, 11: 688794.
[15] JIM?NEZ A P, TRAUM A, BOETTGER T, et al.The tumor suppressor RASSF1A induces the YAP1 target gene ANKRD1 that is epigenetically inactivated in human cancers and inhibits tumor growth[J].Oncotarget, 2017, 8(51): 88437-88452.

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备注/Memo

备注/Memo:
基金项目：复旦大学附属中山医院厦门医院科研孵化课题（2020ZSXMY526）。
作者简介：姜秋利（1988-），女，硕士，主治医师，研究方向：临床病理，E-mail:741958123@qq.com。
通讯作者：许建芳（1959-），女，本科，主任医师，研究方向：临床病理，E-mail：xu.jianfang@zs-hospital.sh.cn。
更新日期/Last Update: 2023-01-15