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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

KIBRA; a novel biomarker predicting recurrence free survival of breast cancer patients receiving adjuvant therapy

Authors: Lakmini Mudduwa, Harshini Peiris, Shania Gunasekara, Deepthika Abeysiriwardhana, Nimsha Liyanage, Suresh K. Rayala, Thusharie Liyanage

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

This study was carried out to evaluate the prognostic value of KIBRA in breast cancer.

Methods

This retrospective study included breast cancer patients who sought the services of the immunohistochemistry laboratory of our unit from 2006 to 2015. Tissue microarrays were constructed and immunohistochemical staining was done to assess the KIBRA expression. The Kaplan-Meier model for univariate and Cox-regression model with backward stepwise factor retention method for multivariate analyses were used. Chi square test was used to find out the associations with the established prognostic features.

Results

A total of 1124 patients were included in the study and KIBRA staining of 909 breast cancers were available for analysis. Cytoplasmic KIBRA expression was seen in 39.5% and nuclear expression in 44.8%. Overall KIBRA–low breast cancers accounted for 41.5%. KIBRA nuclear expression was significantly associated with positive ER and PR expression. Luminal breast cancer patients who had endocrine therapy and KIBRA-low expression had a RFS disadvantage over those who were positive for KIBRA (p = 0.02). Similarly, patients who received chemotherapy and had overall KIBRA-low expression also demonstrated a RFS disadvantage compared to those who had overall positive KIBRA expression (p = 0.018). This effect of KIBRA was independent of the other factors considered for the model.

Conclusion

Overall low-KIBRA expression has an independent effect on the RFS and predicts the RFS outcome of luminal breast cancer patients who received endocrine therapy and breast cancer patients who received chemotherapy.
Literature
1.
go back to reference Kos Z, Dabbs DJ. Biomarker assessment and molecular testing for prognostication in breast cancer. Histopathology. 2016;68:70–85.CrossRefPubMed Kos Z, Dabbs DJ. Biomarker assessment and molecular testing for prognostication in breast cancer. Histopathology. 2016;68:70–85.CrossRefPubMed
3.
go back to reference Rayala SK, den Hollander P, Manavathi B, et al. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006;281:19092–9.CrossRefPubMed Rayala SK, den Hollander P, Manavathi B, et al. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006;281:19092–9.CrossRefPubMed
4.
go back to reference Mavuluri J, Beesetti S, Surabhi R, et al. Phosphorylation dependent regulation of DNA damage response of adaptor protein KIBRA in cancer cells. Mol Cell Biol. 2016;36:1354–65.CrossRefPubMedPubMedCentral Mavuluri J, Beesetti S, Surabhi R, et al. Phosphorylation dependent regulation of DNA damage response of adaptor protein KIBRA in cancer cells. Mol Cell Biol. 2016;36:1354–65.CrossRefPubMedPubMedCentral
5.
go back to reference Füzéry AK, Levin J, Chan MM, et al. Translation proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges. Clin Proteomics. 2013;10:13.CrossRefPubMedPubMedCentral Füzéry AK, Levin J, Chan MM, et al. Translation proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges. Clin Proteomics. 2013;10:13.CrossRefPubMedPubMedCentral
6.
7.
go back to reference Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn H-J, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol. 2007;18:1133–44.CrossRefPubMed Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn H-J, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol. 2007;18:1133–44.CrossRefPubMed
10.
go back to reference Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer; 2009. p. 419–60. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer; 2009. p. 419–60.
11.
go back to reference Kremerskothen J, Plaas C, Buther K, et al. Characterization of KIBRA, a novel WW domain-containing protein. Biochem Biophys Res Commun. 2003;300(4):862–7.CrossRefPubMed Kremerskothen J, Plaas C, Buther K, et al. Characterization of KIBRA, a novel WW domain-containing protein. Biochem Biophys Res Commun. 2003;300(4):862–7.CrossRefPubMed
12.
go back to reference Papassotiropoulos A, Stephan DA, Huentelman MJ, et al. Common Kibra alleles are associated with human memory performance. Science. 2006;314(5798):475–8.CrossRefPubMed Papassotiropoulos A, Stephan DA, Huentelman MJ, et al. Common Kibra alleles are associated with human memory performance. Science. 2006;314(5798):475–8.CrossRefPubMed
13.
go back to reference Johannsen S, Dunig K, Pavenstadt H, et al. Temporal-spatial expression and novel biochemical properties of the memory=related protein KIBRA. Neuroscience. 2008;155(4):1165–73.CrossRefPubMed Johannsen S, Dunig K, Pavenstadt H, et al. Temporal-spatial expression and novel biochemical properties of the memory=related protein KIBRA. Neuroscience. 2008;155(4):1165–73.CrossRefPubMed
15.
go back to reference Hilton HN, Stanford PM, Harris J, et al. KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signaling. Biochem Biopys Acta. 2008;1783(3):383–93.CrossRef Hilton HN, Stanford PM, Harris J, et al. KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signaling. Biochem Biopys Acta. 2008;1783(3):383–93.CrossRef
18.
go back to reference Anuj, Arivazhagan L, Surabhi RP, et al. KIBRA attains oncogenic activity by repressing RASSF1A. Br J Cancer. 2017;117(4):553–62.CrossRef Anuj, Arivazhagan L, Surabhi RP, et al. KIBRA attains oncogenic activity by repressing RASSF1A. Br J Cancer. 2017;117(4):553–62.CrossRef
Metadata
Title
KIBRA; a novel biomarker predicting recurrence free survival of breast cancer patients receiving adjuvant therapy
Authors
Lakmini Mudduwa
Harshini Peiris
Shania Gunasekara
Deepthika Abeysiriwardhana
Nimsha Liyanage
Suresh K. Rayala
Thusharie Liyanage
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4491-6

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