Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers: Companion diagnostics for personalized medicine
Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer patients. In particular, we directly assessed whether nuclear-derived mRNA species encoding proteins involved in mitochondrial protein translation...
Gespeichert in:
| Veröffentlicht in: | Oncotarget Jg. 8; H. 40; S. 67117 |
|---|---|
| Hauptverfasser: | , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
15.09.2017
|
| Schlagworte: | |
| ISSN: | 1949-2553, 1949-2553 |
| Online-Zugang: | Weitere Angaben |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer patients. In particular, we directly assessed whether nuclear-derived mRNA species encoding proteins involved in mitochondrial protein translation and OXPHOS are able to successfully predict clinical outcome in gastric cancer. As such, using
validation, we have now established the prognostic value of these mitochondrial biomarkers, in a defined population of gastric cancer patients. In this context, we interrogated 5 year follow-up data collected from a group of N = 359 gastric cancer patients. Importantly, in this group of cancer patients, Ki67 and PCNA (conventional markers of cell proliferation) were associated with tumor progression, as might be expected. Using this simplified informatics approach, we identified ∼75 new individual mitochondrial gene probes that effectively predicted tumor progression, with hazard-ratios (HR) of up to 2.22 (
< 2.1e-10). These mitochondrial mRNA transcripts included heat shock proteins/chaperones, membrane proteins, anti-oxidants, enzymes involved in genome maintenance, as well as mitochondrial ribosomal proteins (MRPs) and numerous members of the OXPHOS complexes. In addition, we combined 8 mitochondrial protein transcripts (NDUFS5, VDAC3, ATP5O, IMMT, MRPL28, COX5B, MRPL52, PRKDC), to generate a compact gastric mitochondrial gene signature, associated with a HR of 2.77 (
= 1.4e-14). As a result of this analysis and validation, we strongly suggest that proteins involved in mitochondrial protein translation and OXPHOS should be considered as targets for new drug discovery, for the treatment of gastric cancers. The mitochondrial markers we identified here could also be used as companion diagnostics, to predict clinical outcomes, as well as the patient response to therapy. This should allow a more successful and personalized approach to gastric cancer diagnosis and therapy. |
|---|---|
| AbstractList | Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer patients. In particular, we directly assessed whether nuclear-derived mRNA species encoding proteins involved in mitochondrial protein translation and OXPHOS are able to successfully predict clinical outcome in gastric cancer. As such, using in silico validation, we have now established the prognostic value of these mitochondrial biomarkers, in a defined population of gastric cancer patients. In this context, we interrogated 5 year follow-up data collected from a group of N = 359 gastric cancer patients. Importantly, in this group of cancer patients, Ki67 and PCNA (conventional markers of cell proliferation) were associated with tumor progression, as might be expected. Using this simplified informatics approach, we identified ∼75 new individual mitochondrial gene probes that effectively predicted tumor progression, with hazard-ratios (HR) of up to 2.22 (p < 2.1e-10). These mitochondrial mRNA transcripts included heat shock proteins/chaperones, membrane proteins, anti-oxidants, enzymes involved in genome maintenance, as well as mitochondrial ribosomal proteins (MRPs) and numerous members of the OXPHOS complexes. In addition, we combined 8 mitochondrial protein transcripts (NDUFS5, VDAC3, ATP5O, IMMT, MRPL28, COX5B, MRPL52, PRKDC), to generate a compact gastric mitochondrial gene signature, associated with a HR of 2.77 (p = 1.4e-14). As a result of this analysis and validation, we strongly suggest that proteins involved in mitochondrial protein translation and OXPHOS should be considered as targets for new drug discovery, for the treatment of gastric cancers. The mitochondrial markers we identified here could also be used as companion diagnostics, to predict clinical outcomes, as well as the patient response to therapy. This should allow a more successful and personalized approach to gastric cancer diagnosis and therapy.Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer patients. In particular, we directly assessed whether nuclear-derived mRNA species encoding proteins involved in mitochondrial protein translation and OXPHOS are able to successfully predict clinical outcome in gastric cancer. As such, using in silico validation, we have now established the prognostic value of these mitochondrial biomarkers, in a defined population of gastric cancer patients. In this context, we interrogated 5 year follow-up data collected from a group of N = 359 gastric cancer patients. Importantly, in this group of cancer patients, Ki67 and PCNA (conventional markers of cell proliferation) were associated with tumor progression, as might be expected. Using this simplified informatics approach, we identified ∼75 new individual mitochondrial gene probes that effectively predicted tumor progression, with hazard-ratios (HR) of up to 2.22 (p < 2.1e-10). These mitochondrial mRNA transcripts included heat shock proteins/chaperones, membrane proteins, anti-oxidants, enzymes involved in genome maintenance, as well as mitochondrial ribosomal proteins (MRPs) and numerous members of the OXPHOS complexes. In addition, we combined 8 mitochondrial protein transcripts (NDUFS5, VDAC3, ATP5O, IMMT, MRPL28, COX5B, MRPL52, PRKDC), to generate a compact gastric mitochondrial gene signature, associated with a HR of 2.77 (p = 1.4e-14). As a result of this analysis and validation, we strongly suggest that proteins involved in mitochondrial protein translation and OXPHOS should be considered as targets for new drug discovery, for the treatment of gastric cancers. The mitochondrial markers we identified here could also be used as companion diagnostics, to predict clinical outcomes, as well as the patient response to therapy. This should allow a more successful and personalized approach to gastric cancer diagnosis and therapy. Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer patients. In particular, we directly assessed whether nuclear-derived mRNA species encoding proteins involved in mitochondrial protein translation and OXPHOS are able to successfully predict clinical outcome in gastric cancer. As such, using validation, we have now established the prognostic value of these mitochondrial biomarkers, in a defined population of gastric cancer patients. In this context, we interrogated 5 year follow-up data collected from a group of N = 359 gastric cancer patients. Importantly, in this group of cancer patients, Ki67 and PCNA (conventional markers of cell proliferation) were associated with tumor progression, as might be expected. Using this simplified informatics approach, we identified ∼75 new individual mitochondrial gene probes that effectively predicted tumor progression, with hazard-ratios (HR) of up to 2.22 ( < 2.1e-10). These mitochondrial mRNA transcripts included heat shock proteins/chaperones, membrane proteins, anti-oxidants, enzymes involved in genome maintenance, as well as mitochondrial ribosomal proteins (MRPs) and numerous members of the OXPHOS complexes. In addition, we combined 8 mitochondrial protein transcripts (NDUFS5, VDAC3, ATP5O, IMMT, MRPL28, COX5B, MRPL52, PRKDC), to generate a compact gastric mitochondrial gene signature, associated with a HR of 2.77 ( = 1.4e-14). As a result of this analysis and validation, we strongly suggest that proteins involved in mitochondrial protein translation and OXPHOS should be considered as targets for new drug discovery, for the treatment of gastric cancers. The mitochondrial markers we identified here could also be used as companion diagnostics, to predict clinical outcomes, as well as the patient response to therapy. This should allow a more successful and personalized approach to gastric cancer diagnosis and therapy. |
| Author | Lisanti, Michael P Sotgia, Federica |
| Author_xml | – sequence: 1 givenname: Federica surname: Sotgia fullname: Sotgia, Federica organization: Translational Medicine, School of Environment & Life Sciences, Biomedical Research Centre, University of Salford, Greater Manchester, United Kingdom – sequence: 2 givenname: Michael P surname: Lisanti fullname: Lisanti, Michael P organization: Translational Medicine, School of Environment & Life Sciences, Biomedical Research Centre, University of Salford, Greater Manchester, United Kingdom |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28978020$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNUMlOwzAQtRCIltIP4IJ85JISO0tjbqhik4q4wDlyxpNgSOxiO5XgK_hkXFEk5jLbmzcz74QcGmuQkDOWLlhVZvzSGrBBug7DgglR8gMyZSIXCS-K7PBfPCFz79_SaEW-rLg4JhNeiWWV8nRKvh91sPBqjXJa9rTRdpDuHZ2nG4dKQ6BhHKyLme0ceq-todIourGxaLfoZN9TP7qt3sZxbWgnfXAaKEgDkeaKruywkWY3p7TsjPVBg6ftjjP2rZG9_kJFh902bfCUHLWy9zjf-xl5ub15Xt0n66e7h9X1OoG8LELCmyaDJi0Y5i0UWaaYVNCihFQogLJkJU-hagrFmzY2GGDOUaRRlLasltjyGbn45Y2ffYzoQz1oD9j30qAdfR2Ry5IVucgj9HwPHZt4Zr1xOor0Wf-pyH8Ame9-ng |
| CitedBy_id | crossref_primary_10_1016_j_humpath_2021_04_007 crossref_primary_10_1093_jb_mvz111 crossref_primary_10_1038_s41598_023_39179_2 crossref_primary_10_1038_s41598_025_08192_y crossref_primary_10_3390_cancers13236036 crossref_primary_10_1186_s12967_023_04035_4 crossref_primary_10_1186_s12859_022_04864_y crossref_primary_10_1016_j_arr_2018_11_003 crossref_primary_10_3389_fonc_2022_829389 crossref_primary_10_1155_2018_3767482 crossref_primary_10_1016_j_gpb_2020_06_012 crossref_primary_10_3390_ijms24054482 crossref_primary_10_1096_fj_202101862R crossref_primary_10_3389_fcell_2023_1168462 crossref_primary_10_3389_ftox_2022_1028309 crossref_primary_10_1186_s12957_024_03581_5 crossref_primary_10_1016_j_tranon_2025_102432 crossref_primary_10_1016_j_leukres_2024_107568 crossref_primary_10_3390_ani12050583 crossref_primary_10_3390_molecules27092857 crossref_primary_10_1016_j_clineuro_2019_105488 crossref_primary_10_1111_iju_14040 crossref_primary_10_12688_f1000research_22391_1 crossref_primary_10_3390_ijms21228879 crossref_primary_10_1016_j_bbadis_2020_166016 crossref_primary_10_1002_cam4_71012 crossref_primary_10_3390_medicina61010096 crossref_primary_10_1074_jbc_RA119_008476 crossref_primary_10_3390_cancers12061646 crossref_primary_10_1016_j_ygeno_2021_02_020 crossref_primary_10_1038_s41598_020_65119_5 crossref_primary_10_1080_15592294_2024_2445447 crossref_primary_10_3892_mco_2021_2365 crossref_primary_10_3390_ijms20194952 crossref_primary_10_1002_1878_0261_13612 crossref_primary_10_1002_jcp_27314 crossref_primary_10_1016_j_gene_2023_147970 crossref_primary_10_1111_1759_7714_13200 |
| ContentType | Journal Article |
| DBID | NPM 7X8 |
| DOI | 10.18632/oncotarget.19962 |
| DatabaseName | PubMed MEDLINE - Academic |
| DatabaseTitle | PubMed MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic PubMed |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| EISSN | 1949-2553 |
| ExternalDocumentID | 28978020 |
| Genre | Journal Article |
| GroupedDBID | --- 53G ADBBV ADRAZ AENEX ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL DIK FRJ GX1 HYE KQ8 M48 NPM OK1 PGMZT RPM 7X8 |
| ID | FETCH-LOGICAL-c465t-2bb3cb051e4fc533d1adcfeac09dcc661620c8b5d2bfdcf1ce42e90194f687ef2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 38 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000410790500028&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1949-2553 |
| IngestDate | Sun Nov 09 14:36:10 EST 2025 Mon Aug 18 08:05:14 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | false |
| IsScholarly | true |
| Issue | 40 |
| Keywords | overall survival mitochondrial biomarkers tumor progression gastric cancer |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c465t-2bb3cb051e4fc533d1adcfeac09dcc661620c8b5d2bfdcf1ce42e90194f687ef2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=19962&path%5B%5D=63708 |
| PMID | 28978020 |
| PQID | 1947615494 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1947615494 pubmed_primary_28978020 |
| PublicationCentury | 2000 |
| PublicationDate | 2017-09-15 |
| PublicationDateYYYYMMDD | 2017-09-15 |
| PublicationDate_xml | – month: 09 year: 2017 text: 2017-09-15 day: 15 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Oncotarget |
| PublicationTitleAlternate | Oncotarget |
| PublicationYear | 2017 |
| References | 28039467 - Oncotarget. 2017 Feb 7;8(6):9868-9884 27220421 - Breast Cancer Res. 2016 May 24;18(1):55 26421710 - Oncotarget. 2015 Oct 13;6(31):30472-86 28462378 - Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):359-366 28411284 - Oncotarget. 2017 Mar 2;8(12 ):20309-20327 28469358 - Ann Gastroenterol. 2017;30(3):287-294 27141887 - Nat Rev Clin Oncol. 2017 Jan;14 (1):11-31 28462377 - Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):348-358 25625193 - Oncotarget. 2015 Mar 10;6(7):4569-84 25415228 - Oncotarget. 2014 Nov 30;5(22):11029-37 27344270 - Aging (Albany NY). 2016 Aug;8(8):1593-607 25668730 - Nat Rev Clin Oncol. 2015 Apr;12(4):190 28462375 - Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):331-338 26087309 - Oncotarget. 2015 Jun 10;6(16):14005-25 27136895 - Oncotarget. 2016 Jun 7;7(23):34084-99 26421711 - Oncotarget. 2015 Oct 13;6(31):30453-71 28447336 - Histol Histopathol. 2017 Apr 27;:11898 28488584 - Oncotarget. 2017 Jul 25;8(30):50273-50283 26087310 - Oncotarget. 2015 Jun 20;6(17 ):14777-95 28223550 - Oncotarget. 2017 Mar 28;8(13):20667-20678 27384994 - Oncotarget. 2016 Aug 2;7(31):49322-49333 |
| References_xml | – reference: 28447336 - Histol Histopathol. 2017 Apr 27;:11898 – reference: 27141887 - Nat Rev Clin Oncol. 2017 Jan;14 (1):11-31 – reference: 27136895 - Oncotarget. 2016 Jun 7;7(23):34084-99 – reference: 27220421 - Breast Cancer Res. 2016 May 24;18(1):55 – reference: 28488584 - Oncotarget. 2017 Jul 25;8(30):50273-50283 – reference: 25668730 - Nat Rev Clin Oncol. 2015 Apr;12(4):190 – reference: 27384994 - Oncotarget. 2016 Aug 2;7(31):49322-49333 – reference: 26087310 - Oncotarget. 2015 Jun 20;6(17 ):14777-95 – reference: 28462378 - Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):359-366 – reference: 25625193 - Oncotarget. 2015 Mar 10;6(7):4569-84 – reference: 28039467 - Oncotarget. 2017 Feb 7;8(6):9868-9884 – reference: 28223550 - Oncotarget. 2017 Mar 28;8(13):20667-20678 – reference: 28462377 - Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):348-358 – reference: 25415228 - Oncotarget. 2014 Nov 30;5(22):11029-37 – reference: 28462375 - Cell Mol Gastroenterol Hepatol. 2017 Feb 20;3(3):331-338 – reference: 26421711 - Oncotarget. 2015 Oct 13;6(31):30453-71 – reference: 26087309 - Oncotarget. 2015 Jun 10;6(16):14005-25 – reference: 26421710 - Oncotarget. 2015 Oct 13;6(31):30472-86 – reference: 27344270 - Aging (Albany NY). 2016 Aug;8(8):1593-607 – reference: 28469358 - Ann Gastroenterol. 2017;30(3):287-294 – reference: 28411284 - Oncotarget. 2017 Mar 2;8(12 ):20309-20327 |
| SSID | ssj0000547829 |
| Score | 2.3656569 |
| Snippet | Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 67117 |
| Title | Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers: Companion diagnostics for personalized medicine |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/28978020 https://www.proquest.com/docview/1947615494 |
| Volume | 8 |
| WOSCitedRecordID | wos000410790500028&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8NAEF7UevDiA1_1xQpel6abzcuLiFg82NKDQm9ln1KoSUxSD_4Kf7IzeehJELzkkLBLSL6d-WZndj5Crpx2LoylY6FThgG_tSyxxmOacxlG3IEXrA8KP0aTSTybJdN2w61syyo7m1gbapNp3CMfQLANETdEM-Imf2OoGoXZ1VZCY530fKAyiOpoFn_vsXjYrKoWKoPRCQP27LeJzTj0-SDD9gd1vTWe2UO9nN9IZu1sRjv_fc1dst3STHrb4GKPrNl0n3yOYfmCuUsNoo7iyXsszilKmheYr6lotXrNClrXbDX9OqhMDc0zuImlnnK5pOUKjAvAky5S-iJR9UNTjdApymvaWBccZ5oSPmwCTR3O2ZH-D2tol9A_IM-j-6e7B9YqMjAtwqBiXClfK1jHVjgNRNEMpdEObLeXGK3B1Yfc07EKDFcOHgy1FdwC40gEACKyjh-SjTRL7TGhMomcsVzGSklhgyjxbBzIwBcwrzAu6ZPL7gPPAfGYxpCpzVbl_OcT98lR85fmedOaYw7hYxQDAz75w-hTssXRR6MeRHBGeg7Wuz0nm_q9WpTFRQ0luE6m4y9gedvT |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mitochondrial+biomarkers+predict+tumor+progression+and+poor+overall+survival+in+gastric+cancers%3A+Companion+diagnostics+for+personalized+medicine&rft.jtitle=Oncotarget&rft.au=Sotgia%2C+Federica&rft.au=Lisanti%2C+Michael+P&rft.date=2017-09-15&rft.eissn=1949-2553&rft.volume=8&rft.issue=40&rft.spage=67117&rft_id=info:doi/10.18632%2Foncotarget.19962&rft_id=info%3Apmid%2F28978020&rft_id=info%3Apmid%2F28978020&rft.externalDocID=28978020 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1949-2553&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1949-2553&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1949-2553&client=summon |