Skip to main content
Top
Published in: Tumor Biology 11/2014

01-11-2014 | Research Article

Lin28 promotes Her2 expression and Lin28/Her2 predicts poorer survival in gastric cancer

Authors: Qinchuan Wang, Jichun Zhou, Jufeng Guo, Rongyue Teng, Jianguo Shen, Yasheng Huang, Shuduo Xie, Qun Wei, Wenhe Zhao, Wenjun Chen, Xiaoming Yuan, Yongxia Chen, Linbo Wang

Published in: Tumor Biology | Issue 11/2014

Login to get access

Abstract

The main purpose of this study is to investigate the interactions between Lin28 and Her2 in gastric cancer. Lin28 and Her2 expression were evaluated in surgically resected samples of 298 gastric cancer patients using immunohistochemical staining. The correlations between Lin28/Her2 expression and clinical variables were retrospectively analyzed. The mRNA level of LIN28 and HER2 was detected by reverse-transcriptase polymerase chain reaction. Among all gastric cancer patients, 33.9 % (101/298) were determined as Her2-positive, and 43.0 % (128/298) were defined as Lin28-positive. Lin28 was significantly associated with Her2, advanced tumor stage, lesion size, and Ki67 level (p < 0.05 for each). Kaplan-Meier analysis illustrated that both Lin28 and Her2 are poor prognostic factors in gastric cancer; Lin28(+)/Her2(+) patients have the poorest survival (median survival = 17 months, p < 0.01). Multivariate Cox analysis showed that Lin28 is a significant prognostic factor (hazard ratio (HR) = 1.79, 95 % confidence interval (CI) 1.23–2.62). Further stratification analysis indicated that Lin28 may be a prognostic factor in chemotherapy. In vitro data on MKN-28 and MKN-45 cells showed that Lin28 can upregulate Her2 expression at translational level. Both Lin28 and Her2 are poor prognostic factors in gastric cancer. Lin28 may regulate Her2 post-transcriptionally in gastric cancer cells, which indicates it might be a potential target in the treatment of gastric cancer.
Appendix
Available only for authorised users
Literature
2.
go back to reference Wong H, Yau T. Targeted therapy in the management of advanced gastric cancer: are we making progress in the era of personalized medicine? Oncologist. 2012;17(3):346–58.PubMedCentralPubMedCrossRef Wong H, Yau T. Targeted therapy in the management of advanced gastric cancer: are we making progress in the era of personalized medicine? Oncologist. 2012;17(3):346–58.PubMedCentralPubMedCrossRef
3.
go back to reference de Gonzalez de Castro D et al. Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance. Clin Pharmacol Ther. 2013;93(3):252–9.PubMedCentralPubMedCrossRef de Gonzalez de Castro D et al. Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance. Clin Pharmacol Ther. 2013;93(3):252–9.PubMedCentralPubMedCrossRef
4.
go back to reference Albain KS et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55–65.PubMedCentralPubMedCrossRef Albain KS et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55–65.PubMedCentralPubMedCrossRef
5.
go back to reference Paik S et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.PubMedCrossRef Paik S et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.PubMedCrossRef
6.
go back to reference Slamon DJ et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.PubMedCrossRef Slamon DJ et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.PubMedCrossRef
7.
8.
go back to reference Ajani JA et al. Gastric cancer. J Natl Compr Canc Netw. 2010;8(4):378–409.PubMed Ajani JA et al. Gastric cancer. J Natl Compr Canc Netw. 2010;8(4):378–409.PubMed
9.
go back to reference Bang YJ et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.PubMedCrossRef Bang YJ et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.PubMedCrossRef
10.
go back to reference Gordon MA et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol. 2013;24(7):1754–61.PubMedCentralPubMedCrossRef Gordon MA et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol. 2013;24(7):1754–61.PubMedCentralPubMedCrossRef
11.
go back to reference Martinez NJ, Gregory RI. MicroRNA gene regulatory pathways in the establishment and maintenance of ESC identity. Cell Stem Cell. 2010;7(1):31–5.PubMedCrossRef Martinez NJ, Gregory RI. MicroRNA gene regulatory pathways in the establishment and maintenance of ESC identity. Cell Stem Cell. 2010;7(1):31–5.PubMedCrossRef
12.
go back to reference Matera AG, Terns RM, Terns MP. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 2007;8(3):209–20.PubMedCrossRef Matera AG, Terns RM, Terns MP. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 2007;8(3):209–20.PubMedCrossRef
14.
15.
go back to reference Peng S, Maihle NJ, Huang Y. Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene. 2010;29(14):2153–9.PubMedCrossRef Peng S, Maihle NJ, Huang Y. Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene. 2010;29(14):2153–9.PubMedCrossRef
16.
go back to reference Oh JS et al. Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. Int J Radiat Oncol Biol Phys. 2010;76(1):5–8.PubMedCrossRef Oh JS et al. Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. Int J Radiat Oncol Biol Phys. 2010;76(1):5–8.PubMedCrossRef
17.
go back to reference Saiki Y et al. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Ann Surg Oncol. 2009;16(9):2638–44.PubMedCrossRef Saiki Y et al. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Ann Surg Oncol. 2009;16(9):2638–44.PubMedCrossRef
18.
go back to reference Xu C et al. Positive expression of Lin28 is correlated with poor survival in gastric carcinoma. Med Oncol. 2013;30(1):382.PubMedCrossRef Xu C et al. Positive expression of Lin28 is correlated with poor survival in gastric carcinoma. Med Oncol. 2013;30(1):382.PubMedCrossRef
19.
go back to reference Piskounova E et al. Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28. J Biol Chem. 2008;283(31):21310–4.PubMedCrossRef Piskounova E et al. Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28. J Biol Chem. 2008;283(31):21310–4.PubMedCrossRef
22.
go back to reference Feng C et al. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle. 2012;11(13):2486–94.PubMedCrossRef Feng C et al. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle. 2012;11(13):2486–94.PubMedCrossRef
24.
go back to reference Teng RY et al. The relationship between Lin28 and the chemotherapy response of gastric cancer. Oncol Targets Ther. 2013;6:1341–5.CrossRef Teng RY et al. The relationship between Lin28 and the chemotherapy response of gastric cancer. Oncol Targets Ther. 2013;6:1341–5.CrossRef
25.
go back to reference Xu CY et al. Prognostic role of estrogen receptor alpha and estrogen receptor beta in gastric cancer. Ann Surg Oncol. 2010;17(9):2503–9.PubMedCrossRef Xu CY et al. Prognostic role of estrogen receptor alpha and estrogen receptor beta in gastric cancer. Ann Surg Oncol. 2010;17(9):2503–9.PubMedCrossRef
26.
go back to reference Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2) 101–12. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2) 101–12.
27.
go back to reference Kim KC et al. Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol. 2011;18(10):2833–40.PubMedCrossRef Kim KC et al. Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol. 2011;18(10):2833–40.PubMedCrossRef
28.
go back to reference Janjigian YY et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012;23(10):2656–62.PubMedCrossRef Janjigian YY et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012;23(10):2656–62.PubMedCrossRef
29.
go back to reference Sakurai M et al. LIN28: a regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer. J Steroid Biochem Mol Biol. 2012;131(3–5):101–6.PubMedCrossRef Sakurai M et al. LIN28: a regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer. J Steroid Biochem Mol Biol. 2012;131(3–5):101–6.PubMedCrossRef
30.
32.
go back to reference Huang Y. A mirror of two faces: Lin28 as a master regulator of both miRNA and mRNA. Wiley Interdiscip Rev RNA. 2012;3(4):483–94.PubMedCrossRef Huang Y. A mirror of two faces: Lin28 as a master regulator of both miRNA and mRNA. Wiley Interdiscip Rev RNA. 2012;3(4):483–94.PubMedCrossRef
33.
go back to reference Fang C, Zhao Y, Guo B. MiR-199b-5p targets HER2 in breast cancer cells. J Cell Biochem. 2013;114(7):1457–63.PubMedCrossRef Fang C, Zhao Y, Guo B. MiR-199b-5p targets HER2 in breast cancer cells. J Cell Biochem. 2013;114(7):1457–63.PubMedCrossRef
34.
go back to reference Fassan M et al. The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis. Hum Pathol. 2013;44(9):1804–10.PubMedCrossRef Fassan M et al. The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis. Hum Pathol. 2013;44(9):1804–10.PubMedCrossRef
Metadata
Title
Lin28 promotes Her2 expression and Lin28/Her2 predicts poorer survival in gastric cancer
Authors
Qinchuan Wang
Jichun Zhou
Jufeng Guo
Rongyue Teng
Jianguo Shen
Yasheng Huang
Shuduo Xie
Qun Wei
Wenhe Zhao
Wenjun Chen
Xiaoming Yuan
Yongxia Chen
Linbo Wang
Publication date
01-11-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2481-0

Other articles of this Issue 11/2014

Tumor Biology 11/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine