• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

蛋白磷酸酶2A的癌性抑制剂（CIP2A）是结直肠癌肝转移切除术后野生型KRAS转移性结直肠癌的独立预后标志物。

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an independent prognostic marker in wild-type KRAS metastatic colorectal cancer after colorectal liver metastasectomy.

作者信息

Chen Kuen-Feng, Yen Chueh-Chuan, Lin Jen-Kou, Chen Wei-Shone, Yang Shung-Haur, Jiang Jeng-Kai, Lan Yuan-Tzu, Lin Chun-Chi, Yu Hui-Chuan, Hsu Hui-Mei, Lin Wen-Ling, Teng Hao-Wei

机构信息

Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.

National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

BMC Cancer. 2015 Apr 17;15:301. doi: 10.1186/s12885-015-1300-3.

DOI:10.1186/s12885-015-1300-3
PMID:25896895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4404594/
Abstract

BACKGROUND

The impact of KRAS signaling on cancerous inhibitor of protein phosphatase 2A (CIP2A) expression has not yet been explored. We investigated the impact of KRAS on CIP2A expression in colorectal cancer patients after colorectal liver metastasectomy.

METHODS

We examined CIP2A expression by immunohistochemistry (IHC) and used direct sequencing to identify the mutational status of KRAS exon 2 (codon 12 and 13). The association between CIP2A expression, KRAS genotype, clinicopathological parameters and survival were examined by the Kaplan-Meier method and the Cox proportional hazards model. A combination of immunoblotting and proliferation assays were employed to elucidate the role of CIP2A in signal transduction pathways in wild-type KRAS Caco-2 cells.

RESULTS

A total of 220 colorectal cancer patients who had undergone colorectal liver metastasectomy were included in the study. The mutant KRAS genotype was associated with CIP2A overexpression. CIP2A expression was an independent prognostic marker in patients with wild-type KRAS metastatic colorectal cancer after colorectal liver metastasectomy (relative risk = 1.873, P = 0.019). Targeted silencing of CIP2A in Caco-2 cells (wild-type KRAS) led to decreased expression of pERK/ERK and decreased cell proliferation. Overexpression of mutant KRAS G12D in Caco-2 cells led to an increase in CIP2A expression and cell proliferation. In Caco-2 cells with the KRAS G12D, KRAS overexpression preserved the regulation effect of CIP2A in KRAS and abrogated the impact of CIP2A regulation on pERK/ERK and cell proliferation. CIP2A inhibition also increased the efficacy of cetuximab in Caco-2 cells.

CONCLUSIONS

CIP2A is an independent prognostic marker in patients with wild-type KRAS metastatic colorectal cancer after colorectal liver metastasectomy.

摘要

背景

KRAS信号传导对蛋白磷酸酶2A癌性抑制剂（CIP2A）表达的影响尚未得到研究。我们调查了KRAS对结直肠癌肝转移切除术后患者CIP2A表达的影响。

方法

我们通过免疫组织化学（IHC）检测CIP2A表达，并使用直接测序法确定KRAS外显子2（密码子12和13）的突变状态。采用Kaplan-Meier法和Cox比例风险模型研究CIP2A表达、KRAS基因型、临床病理参数与生存率之间的关联。采用免疫印迹和增殖试验相结合的方法，阐明CIP2A在野生型KRAS Caco-2细胞信号转导通路中的作用。

结果

本研究共纳入220例接受了结直肠癌肝转移切除术的患者。KRAS突变基因型与CIP2A过表达相关。在结直肠癌肝转移切除术后的野生型KRAS转移性结直肠癌患者中，CIP2A表达是一个独立的预后标志物（相对风险=1.873，P=0.019）。在Caco-2细胞（野生型KRAS）中靶向沉默CIP2A导致pERK/ERK表达降低和细胞增殖减少。在Caco-2细胞中过表达突变型KRAS G12D导致CIP2A表达增加和细胞增殖。在具有KRAS G12D的Caco-2细胞中，KRAS过表达保留了CIP2A对KRAS的调节作用，并消除了CIP2A调节对pERK/ERK和细胞增殖的影响。CIP2A抑制还增强了西妥昔单抗在Caco-2细胞中的疗效。

结论

CIP2A是结直肠癌肝转移切除术后野生型KRAS转移性结直肠癌患者的独立预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/836d0d620af9/12885_2015_1300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/85d21af56fa9/12885_2015_1300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/6425e2fa5dc1/12885_2015_1300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/a553a60a1650/12885_2015_1300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/9ba249178eca/12885_2015_1300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/836d0d620af9/12885_2015_1300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/85d21af56fa9/12885_2015_1300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/6425e2fa5dc1/12885_2015_1300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/a553a60a1650/12885_2015_1300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/9ba249178eca/12885_2015_1300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e384/4404594/836d0d620af9/12885_2015_1300_Fig5_HTML.jpg

相似文献

1
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an independent prognostic marker in wild-type KRAS metastatic colorectal cancer after colorectal liver metastasectomy.蛋白磷酸酶2A的癌性抑制剂（CIP2A）是结直肠癌肝转移切除术后野生型KRAS转移性结直肠癌的独立预后标志物。
BMC Cancer. 2015 Apr 17;15:301. doi: 10.1186/s12885-015-1300-3.
2
BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy.BRAF 突变是结直肠癌肝转移切除术的预后生物标志物。
J Surg Oncol. 2012 Aug 1;106(2):123-9. doi: 10.1002/jso.23063. Epub 2012 Feb 13.
3
CIP2A overexpression is associated with c-Myc expression in colorectal cancer.CIP2A 的过表达与结直肠癌中的 c-Myc 表达相关。
Cancer Biol Ther. 2012 Mar;13(5):289-95. doi: 10.4161/cbt.18922. Epub 2012 Mar 1.
4
KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.转移性结直肠癌患者原发性肿瘤与转移性肿瘤之间的KRAS不一致性。
J BUON. 2015 Jan-Feb;20(1):128-35.
5
KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer.KRAS和BRAF突变是接受结直肠癌肺转移瘤切除术患者的预后生物标志物。
Br J Cancer. 2015 Feb 17;112(4):720-8. doi: 10.1038/bjc.2014.499.
6
[Expression of cancerous inhibitor of protein phosphatase 2A in tissue microarray of colorectal cancer and its clinical significance].
Zhonghua Wei Chang Wai Ke Za Zhi. 2013 Nov;16(11):1102-6.
7
Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism.替西罗莫司通过依赖 CIP2A 的机制增强西妥昔单抗在结肠癌中的疗效。
J Cancer Res Clin Oncol. 2014 Apr;140(4):561-71. doi: 10.1007/s00432-014-1596-4. Epub 2014 Feb 4.
8
Effect of CIP2A and its mechanism of action in the malignant biological behavior of colorectal cancer.CIP2A 在结直肠癌恶性生物学行为中的作用及其作用机制。
Cell Commun Signal. 2020 Apr 22;18(1):67. doi: 10.1186/s12964-020-00545-6.
9
Relationships among mutation status, expression of RAS pathway signaling molecules, and clinicopathological features and prognosis of patients with colorectal cancer.结直肠癌患者突变状态、RAS 通路信号分子表达与临床病理特征和预后的关系。
World J Gastroenterol. 2019 Feb 21;25(7):808-823. doi: 10.3748/wjg.v25.i7.808.
10
EGFR, BRAF and KRAS status in patients undergoing pulmonary metastasectomy from primary colorectal carcinoma: a prospective follow-up study.原发性结直肠癌肺转移患者 EGFR、BRAF 和 KRAS 状态：一项前瞻性随访研究。
Ann Surg Oncol. 2014 Mar;21(3):946-54. doi: 10.1245/s10434-013-3386-7. Epub 2013 Nov 27.

引用本文的文献

1
From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.从基础科学到临床实践：蛋白磷酸酶2A癌性抑制剂（CIP2A）/p90在癌症中的作用
Front Genet. 2023 Feb 24;14:1110656. doi: 10.3389/fgene.2023.1110656. eCollection 2023.
2
The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors.蛋白磷酸酶 2A（PP2A）在脑肿瘤中的关键作用。
Int J Mol Sci. 2022 Dec 11;23(24):15717. doi: 10.3390/ijms232415717.
3
A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC.

本文引用的文献

1
Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism.替西罗莫司通过依赖 CIP2A 的机制增强西妥昔单抗在结肠癌中的疗效。
J Cancer Res Clin Oncol. 2014 Apr;140(4):561-71. doi: 10.1007/s00432-014-1596-4. Epub 2014 Feb 4.
2
[Expression of cancerous inhibitor of protein phosphatase 2A in tissue microarray of colorectal cancer and its clinical significance].
Zhonghua Wei Chang Wai Ke Za Zhi. 2013 Nov;16(11):1102-6.
3
Clinical implications of CIP2A protein expression in breast cancer.CIP2A 蛋白在乳腺癌中的表达的临床意义。
一种新型的 ATOH8 异构体通过调节 RhoC 促进乳腺癌的转移。
J Mol Cell Biol. 2021 Apr 10;13(1):59-71. doi: 10.1093/jmcb/mjaa050.
4
Effect of CIP2A and its mechanism of action in the malignant biological behavior of colorectal cancer.CIP2A 在结直肠癌恶性生物学行为中的作用及其作用机制。
Cell Commun Signal. 2020 Apr 22;18(1):67. doi: 10.1186/s12964-020-00545-6.
5
Prognostic Significance of CIP2A in Esophagogastric Junction Adenocarcinoma: A Study of 65 Patients and a Meta-Analysis.胃食管结合部腺癌中 CIP2A 的预后意义：65 例患者研究和荟萃分析。
Dis Markers. 2019 Aug 22;2019:2312439. doi: 10.1155/2019/2312439. eCollection 2019.
6
ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer.内质网应激相关 ATF6 上调 CIP2A 并导致结肠癌预后不良。
Mol Oncol. 2018 Oct;12(10):1706-1717. doi: 10.1002/1878-0261.12365. Epub 2018 Aug 20.
7
Prognostic significance of CIP2A expression in solid tumors: A meta-analysis.CIP2A 表达在实体瘤中的预后意义：一项荟萃分析。
PLoS One. 2018 Jul 25;13(7):e0199675. doi: 10.1371/journal.pone.0199675. eCollection 2018.
8
Protein phosphatase 2A (PP2A) inhibitor CIP2A indicates resistance to radiotherapy in rectal cancer.蛋白磷酸酶 2A（PP2A）抑制剂 CIP2A 表明直肠癌对放疗有抵抗性。
Cancer Med. 2018 Mar;7(3):698-706. doi: 10.1002/cam4.1361. Epub 2018 Feb 14.
9
Feedback between E2F1 and CIP2A regulated by human papillomavirus E7 in cervical cancer: implications for prognosis.人乳头瘤病毒E7调控的E2F1与CIP2A之间的反馈在宫颈癌中的作用：对预后的影响
Am J Transl Res. 2017 May 15;9(5):2327-2339. eCollection 2017.
Med Oncol. 2013 Jun;30(2):524. doi: 10.1007/s12032-013-0524-9. Epub 2013 Mar 8.
4
CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma.CIP2A 是膀胱癌的一个生存预测因子和一个新的治疗靶点。
Med Oncol. 2013 Mar;30(1):406. doi: 10.1007/s12032-012-0406-6. Epub 2012 Dec 30.
5
Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR activity.开发厄洛替尼衍生物作为独立于 EGFR 活性的 CIP2A 消融剂。
Bioorg Med Chem. 2012 Oct 15;20(20):6144-53. doi: 10.1016/j.bmc.2012.08.039. Epub 2012 Aug 30.
6
CIP2A is overexpressed in human ovarian cancer and regulates cell proliferation and apoptosis.CIP2A在人类卵巢癌中过度表达，并调节细胞增殖和凋亡。
Tumour Biol. 2012 Dec;33(6):2299-306. doi: 10.1007/s13277-012-0492-2. Epub 2012 Aug 25.
7
CIP2A is highly expressed in hepatocellular carcinoma and predicts poor prognosis.CIP2A在肝细胞癌中高表达，并预示预后不良。
Diagn Mol Pathol. 2012 Sep;21(3):143-9. doi: 10.1097/PDM.0b013e318249fd8b.
8
CIP2A is a target of bortezomib in human triple negative breast cancer cells.CIP2A 是硼替佐米在人三阴性乳腺癌细胞中的作用靶点。
Breast Cancer Res. 2012 Apr 26;14(2):R68. doi: 10.1186/bcr3175.
9
CIP2A-mediated Akt activation plays a role in bortezomib-induced apoptosis in head and neck squamous cell carcinoma cells.CIP2A 介导的 Akt 激活在硼替佐米诱导的头颈部鳞状细胞癌细胞凋亡中起作用。
Oral Oncol. 2012 Jul;48(7):585-93. doi: 10.1016/j.oraloncology.2012.01.012. Epub 2012 Feb 17.
10
BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy.BRAF 突变是结直肠癌肝转移切除术的预后生物标志物。
J Surg Oncol. 2012 Aug 1;106(2):123-9. doi: 10.1002/jso.23063. Epub 2012 Feb 13.