Abnormal expression of ATP1A1 and ATP1A2 in breast cancer

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Moiseenko" }, { "@type": "Person", "name": "Michael Dubina" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Breast cancer is the first in incidence and the second in death among all solid tumors occurring in women. The identification of molecular genetic abnormalities in breast cancer is important to improve the results of treatment. In the present study, we analyzed microarray data of breast cancer expression profiling (NCBI GEO database, accession GSE65194), focusing on Na+/K+-ATPase coding genes. We found overexpression of the ATP1A1 and down-regulation of the ATP1A2. We expect that our research could help to improve the understanding of predictive and prognostic features of breast cancer." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/6-10/v1", "name": "Abnormal expression of ATP1A1 and ATP1A2 in breast cancer" } } ] } Home Browse Abnormal expression of ATP1A1 and ATP1A2 in breast cancer ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Bogdanov A, Moiseenko FV and Dubina M. Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.12688/f1000research.10481.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Note Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] Alexey Bogdanov https://orcid.org/0000-0002-7887-4635 1-4 , Fedor V. Moiseenko 1,2 , Michael Dubina 1-3 Alexey Bogdanov https://orcid.org/0000-0002-7887-4635 1-4 , Fedor V. Moiseenko 1,2 , Michael Dubina 1-3 PUBLISHED 05 Jan 2017 Author details Author details 1 St Petersburg Academic University, St. Petersburg, Russian Federation 2 Practical Center for Specialized Types of Medical Care (Oncologic), St-Petersburg, Russian Federation 3 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation 4 The Petersburg Nuclear Physics Institute, Gatchina, Russian Federation OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Breast cancer is the first in incidence and the second in death among all solid tumors occurring in women. The identification of molecular genetic abnormalities in breast cancer is important to improve the results of treatment. In the present study, we analyzed microarray data of breast cancer expression profiling (NCBI GEO database, accession GSE65194 ), focusing on Na + /K + -ATPase coding genes. We found overexpression of the ATP1A1 and down-regulation of the ATP1A2 . We expect that our research could help to improve the understanding of predictive and prognostic features of breast cancer. READ ALL READ LESS Keywords breast cancer, Na+/K+-ATPase, gene expression, abnormality, ATP1A1, ATP1A2 Corresponding Author(s) Alexey Bogdanov ( [email protected] ) Fedor V. Moiseenko ( [email protected] ) Close Corresponding authors: Alexey Bogdanov, Fedor V. Moiseenko Competing interests: No competing interests were disclosed. Grant information: This work was supported by The Ministry of Education and Science of Russian Federation (unique identifier of applied research: RFMEFI60414X0070) Copyright: © 2017 Bogdanov A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Bogdanov A, Moiseenko FV and Dubina M. Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.12688/f1000research.10481.1 ) First published: 05 Jan 2017, 6 :10 ( https://doi.org/10.12688/f1000research.10481.1 ) Latest published: 05 Jan 2017, 6 :10 ( https://doi.org/10.12688/f1000research.10481.1 ) Introduction Breast cancer is one of the most common and deadly female solid tumors 1 . According to reports from Perou et al . 2 , further confirmed by other investigators 3 , 4 , breast cancer is a highly molecularly heterogeneous disease. The identification of molecular genetic abnormalities in breast cancer is important to improve the results of treatment and, for instance, to reveal new targets for specific therapies. Recent studies based on original retrospective analysis of digitalis use in breast cancer patients have demonstrated the anticancer effect of cardiac glycosides 5 that directly inhibit Na + /K + -ATPase (NKA) activity. NKA signaling functions after interaction with cardiac glycosides were also shown 6 . It seems rational that expression of NKA might influence breast cancer prognosis. NKA is a significant integral membrane protein. NKA’s main function is the creation and maintenance of electrochemical gradients for sodium and potassium ions in the living cell. These gradients have critical importance for control of cell volume, osmolarity and resting potential 7 , 8 . The minimal functional NKA consists of two associated alpha- and beta- subunits. The catalytic alpha-subunit is responsible for conversion of ATP energy to transport of Na + and K + across cell membranes and has ATP and cardiac glycosides binding sites. It may be present in human tissues in four different isoforms (α1, α2, α3, α4 – found only in testicles). The beta-subunit is responsible for delivery and insertion of alpha one in cell membranes and has three distinct isoforms in humans (β1, β2, β3) 8 – 10 . NKA subunits are variably expressed in different human tissues 11 . Changes in the relative expression between different isoforms are associated with a number of pathological processes including malignant transformation 12 , 13 . Both down- and up-regulation of alpha- and beta- subunits were shown in solid tumors of different origin 14 – 19 . In the present study, we analyzed public breast cancer expression profiles made using Affymetrix Human Genome U133 Plus 2.0 Array (NCBI GEO database 20 , accession GSE65194 ) for the expression of alpha subunits of NKA. We found abnormalities in ATP1A1 (coding α1-subunit) and ATP1A2 (coding α2-subunit) expression ( Table 1 ) in breast cancer samples relative to their expression in normal breast tissue. ATP1A1 was overexpressed approximately 1.5 times in all groups of breast cancer samples (p<0.05). Coincidently, ATP1A2 expression decreased by more than 2 times (p<0.05). There were no differences observed in the expression of ATP1A3 (coding α3-subunit). Table 1. NKA genes expression in breast cancer samples relative to normal breast tissue. Breast cancer group Lum A Lum B Her2 TNBC Gene Relative expression/(ANOVA P-value) ATP1A1 1.53 (0.009016) 1.38 (0.04454) 1.66 (0.005926) 1.44 (0.015725) ATP1A2 -2.49 (1.85·10 -07 ) -2.52 (8.50·10 -09 ) -2.78 (5.48·10 -08 ) -2.87 (2.08·10-11) ATP1A3 -1.05 (0.429089) 1.03 (0.308298) -1.04 (0.768041) -1.04 (0.527878) Methods Preanalytical procedures consisted of a robust multichip analysis (RMA) algorithm 21 , including background correction, probe set signal integration, and quantile normalization. For this purpose, we used Expression Console 1.4 software (Affymetrix, Inc. USA). We utilized Transcriptome Analysis Console 3.0 software (Affymetrix, Inc. USA) to analyze the obtained CHP files and to detect differentially expressed genes using one-way between subjects ANOVA. Array data for 41 triple negative samples (TNBC group), 30 Her2-positive (Her2 group), 30 Luminal B (Lum B group), 29 Luminal A (Lum A group) breast cancer samples and 11 normal breast tissue samples were investigated. Conclusions Using a public microarray dataset we found abnormalities in the expression of ATP1A1 and ATP1A2 in breast cancer samples. This may correlate with digitalis anticancer activity, but requires additional research. We expect that our research could help to improve the understanding of predictive and prognostic features of breast cancer. Data and software availability Raw data for Table 1 are available at: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE65194&format=file 22 . Expression Console 1.4 software and Transcriptome Analysis Console 3.0 software (Affymetrix, Inc. USA) are available after free customer registration at: http://www.affymetrix.com/support/technical/software_downloads.affx . Author contributions AB, FM and MD conceptualized the study, collected data and performed data analysis. All authors were involved in the writing and revision of the draft manuscript and have agreed to the final content. Competing interests No competing interests were disclosed. Grant information This work was supported by The Ministry of Education and Science of Russian Federation (unique identifier of applied research: RFMEFI60414X0070). F1000 recommended References 1. Siegel RL, Miller KD, Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 2016; 66 (1): 7–30. PubMed Abstract | Publisher Full Text 2. Perou CM, Sørlie T, Eisen MB, et al. : Molecular portraits of human breast tumours. Nature. 2000; 406 (6797): 747–52. PubMed Abstract | Publisher Full Text 3. Sørlie T, Perou CM, Tibshirani R, et al. : Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001; 98 (19): 10869–74. 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Reference Source Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 05 Jan 2017 ADD YOUR COMMENT Comment Author details Author details 1 St Petersburg Academic University, St. Petersburg, Russian Federation 2 Practical Center for Specialized Types of Medical Care (Oncologic), St-Petersburg, Russian Federation 3 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation 4 The Petersburg Nuclear Physics Institute, Gatchina, Russian Federation Competing interests No competing interests were disclosed. Grant information This work was supported by The Ministry of Education and Science of Russian Federation (unique identifier of applied research: RFMEFI60414X0070) Article Versions (1) version 1 Published: 05 Jan 2017, 6:10 https://doi.org/10.12688/f1000research.10481.1 Copyright © 2017 Bogdanov A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Bogdanov A, Moiseenko FV and Dubina M. Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.12688/f1000research.10481.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 05 Jan 2017 Views 0 Cite How to cite this report: Chi JTA. Reviewer Report For: Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.5256/f1000research.11294.r21728 ) The direct URL for this report is: https://f1000research.com/articles/6-10/v1#referee-response-21728 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 May 2017 Jen-Tsan Ashley Chi , Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, 27708, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.11294.r21728 I think the analysis is appropriate to examine the relative expression of the ATP1A1 and ATP1A2 among different breast cancer cells. The data analysis is standard and appropriate. One helpful thing is to validate the findings in other breast cancer ... Continue reading READ ALL I think the analysis is appropriate to examine the relative expression of the ATP1A1 and ATP1A2 among different breast cancer cells. The data analysis is standard and appropriate. One helpful thing is to validate the findings in other breast cancer expression datasets beyond this discovery dataset. Another relevant thing is whether the abnormal expression of these genes are associated with varying clinical outcomes. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Chi JTA. Reviewer Report For: Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.5256/f1000research.11294.r21728 ) The direct URL for this report is: https://f1000research.com/articles/6-10/v1#referee-response-21728 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Fedyanin M. Reviewer Report For: Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.5256/f1000research.11294.r20402 ) The direct URL for this report is: https://f1000research.com/articles/6-10/v1#referee-response-20402 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Feb 2017 Mikhail Fedyanin , Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation Approved VIEWS 0 https://doi.org/10.5256/f1000research.11294.r20402 Over the past years several papers were published concerning prognostic role of ATP1A1 expression in hepatocellular carcinoma, lung cancer, and esophageal cancer. The authors of the present study show that increased expression of ATP1A1 observed at all breast cancer phenotypes ... Continue reading READ ALL Over the past years several papers were published concerning prognostic role of ATP1A1 expression in hepatocellular carcinoma, lung cancer, and esophageal cancer. The authors of the present study show that increased expression of ATP1A1 observed at all breast cancer phenotypes compared to normal tissue. I would like to note that the authors studied gene expression only, but did not appreciate the immunohistochemical (IHC) changes in the content of gene products. In the absence of data of the IHC expression of ATP1A1 , it is desirable to represent the differences in gene expression of ATP1A1 compared to referent genes for membrane transporters ( http://bmcmolbiol.biomedcentral.com/articles/10.1186/1471-2199-7-29 ). Given a sufficiently large number of patients included in the study, it is interesting to evaluate the prognostic and predictive value of these findings. But I can conclude that this article is interesting for medical oncologists and molecular biologists. Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Fedyanin M. Reviewer Report For: Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.5256/f1000research.11294.r20402 ) The direct URL for this report is: https://f1000research.com/articles/6-10/v1#referee-response-20402 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 05 Jan 2017 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 05 Jan 17 read read Mikhail Fedyanin , N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation Jen-Tsan Ashley Chi , Duke University Medical Center, Durham, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2017 Chi J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 May 2017 | for Version 1 Jen-Tsan Ashley Chi , Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, 27708, USA 0 Views copyright © 2017 Chi J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I think the analysis is appropriate to examine the relative expression of the ATP1A1 and ATP1A2 among different breast cancer cells. The data analysis is standard and appropriate. One helpful thing is to validate the findings in other breast cancer expression datasets beyond this discovery dataset. Another relevant thing is whether the abnormal expression of these genes are associated with varying clinical outcomes. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Chi JTA. Peer Review Report For: Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.5256/f1000research.11294.r21728) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/6-10/v1#referee-response-21728 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2017 Fedyanin M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Feb 2017 | for Version 1 Mikhail Fedyanin , Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation 0 Views copyright © 2017 Fedyanin M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Over the past years several papers were published concerning prognostic role of ATP1A1 expression in hepatocellular carcinoma, lung cancer, and esophageal cancer. The authors of the present study show that increased expression of ATP1A1 observed at all breast cancer phenotypes compared to normal tissue. I would like to note that the authors studied gene expression only, but did not appreciate the immunohistochemical (IHC) changes in the content of gene products. In the absence of data of the IHC expression of ATP1A1 , it is desirable to represent the differences in gene expression of ATP1A1 compared to referent genes for membrane transporters ( http://bmcmolbiol.biomedcentral.com/articles/10.1186/1471-2199-7-29 ). Given a sufficiently large number of patients included in the study, it is interesting to evaluate the prognostic and predictive value of these findings. But I can conclude that this article is interesting for medical oncologists and molecular biologists. Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Fedyanin M. Peer Review Report For: Abnormal expression of ATP1A1 and ATP1A2 in breast cancer [version 1; peer review: 2 approved] . F1000Research 2017, 6 :10 ( https://doi.org/10.5256/f1000research.11294.r20402) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/6-10/v1#referee-response-20402 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });