Cargando…
TIMP1 is an early biomarker for detection and prognosis of lung cancer
BACKGROUND: Lung cancer remains the major cause of cancer‐related deaths worldwide. Early stages of lung cancer are characterized by long asymptomatic periods that are ineffectively identified with the current screening programs. This deficiency represents a lost opportunity to improve the overall s...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533479/ https://www.ncbi.nlm.nih.gov/pubmed/37759102 http://dx.doi.org/10.1002/ctm2.1391 |
_version_ | 1785112191223988224 |
---|---|
author | Dantas, Ezequiel Murthy, Anirudh Ahmed, Tanvir Ahmed, Mujmmail Ramsamooj, Shakti Hurd, Maurice A. Lam, Tiffany Malbari, Murtaza Agrusa, Christopher Elemento, Olivier Zhang, Chen Pappin, Darryl J. McGraw, Timothy E. Stiles, Brendon M. Altorki, Nasser K. Goncalves, Marcus D. |
author_facet | Dantas, Ezequiel Murthy, Anirudh Ahmed, Tanvir Ahmed, Mujmmail Ramsamooj, Shakti Hurd, Maurice A. Lam, Tiffany Malbari, Murtaza Agrusa, Christopher Elemento, Olivier Zhang, Chen Pappin, Darryl J. McGraw, Timothy E. Stiles, Brendon M. Altorki, Nasser K. Goncalves, Marcus D. |
author_sort | Dantas, Ezequiel |
collection | PubMed |
description | BACKGROUND: Lung cancer remains the major cause of cancer‐related deaths worldwide. Early stages of lung cancer are characterized by long asymptomatic periods that are ineffectively identified with the current screening programs. This deficiency represents a lost opportunity to improve the overall survival of patients. Serum biomarkers are among the most effective strategies for cancer screening and follow up. METHODS: Using bead‐based multiplexing assays we screened plasma and tumours of the KrasG12D/+; Lkb1f/f (KL) mouse model of lung cancer for cytokines that could be used as biomarkers. We identified tissue inhibitor of metalloproteinase 1 (TIMP1) as an early biomarker and validated this finding in the plasma of lung cancer patients. We used immunohistochemistry (IHC), previously published single‐cell RNA‐seq and bulk RNA‐seq data to assess the source and expression of TIMP1in the tumour. The prognostic value of TIMP1 was assessed using publicly available human proteomic and transcriptomic databases. RESULTS: We found that TIMP1 is a tumour‐secreted protein with high sensitivity and specificity for aggressive cancer, even at early stages in mice. We showed that TIMP1 levels in the tumour and serum correlate with tumour burden and worse survival in mice. We validated this finding using clinical samples from our institution and publicly available human proteomic and transcriptomic databases. These data support the finding that high tumour expression of TIMP1 correlates with an unfavorable prognosis in lung cancer patients. CONCLUSION: TIMP1 is a suitable biomarker for lung cancer detection. |
format | Online Article Text |
id | pubmed-10533479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105334792023-09-29 TIMP1 is an early biomarker for detection and prognosis of lung cancer Dantas, Ezequiel Murthy, Anirudh Ahmed, Tanvir Ahmed, Mujmmail Ramsamooj, Shakti Hurd, Maurice A. Lam, Tiffany Malbari, Murtaza Agrusa, Christopher Elemento, Olivier Zhang, Chen Pappin, Darryl J. McGraw, Timothy E. Stiles, Brendon M. Altorki, Nasser K. Goncalves, Marcus D. Clin Transl Med Research Articles BACKGROUND: Lung cancer remains the major cause of cancer‐related deaths worldwide. Early stages of lung cancer are characterized by long asymptomatic periods that are ineffectively identified with the current screening programs. This deficiency represents a lost opportunity to improve the overall survival of patients. Serum biomarkers are among the most effective strategies for cancer screening and follow up. METHODS: Using bead‐based multiplexing assays we screened plasma and tumours of the KrasG12D/+; Lkb1f/f (KL) mouse model of lung cancer for cytokines that could be used as biomarkers. We identified tissue inhibitor of metalloproteinase 1 (TIMP1) as an early biomarker and validated this finding in the plasma of lung cancer patients. We used immunohistochemistry (IHC), previously published single‐cell RNA‐seq and bulk RNA‐seq data to assess the source and expression of TIMP1in the tumour. The prognostic value of TIMP1 was assessed using publicly available human proteomic and transcriptomic databases. RESULTS: We found that TIMP1 is a tumour‐secreted protein with high sensitivity and specificity for aggressive cancer, even at early stages in mice. We showed that TIMP1 levels in the tumour and serum correlate with tumour burden and worse survival in mice. We validated this finding using clinical samples from our institution and publicly available human proteomic and transcriptomic databases. These data support the finding that high tumour expression of TIMP1 correlates with an unfavorable prognosis in lung cancer patients. CONCLUSION: TIMP1 is a suitable biomarker for lung cancer detection. John Wiley and Sons Inc. 2023-09-27 /pmc/articles/PMC10533479/ /pubmed/37759102 http://dx.doi.org/10.1002/ctm2.1391 Text en © 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Dantas, Ezequiel Murthy, Anirudh Ahmed, Tanvir Ahmed, Mujmmail Ramsamooj, Shakti Hurd, Maurice A. Lam, Tiffany Malbari, Murtaza Agrusa, Christopher Elemento, Olivier Zhang, Chen Pappin, Darryl J. McGraw, Timothy E. Stiles, Brendon M. Altorki, Nasser K. Goncalves, Marcus D. TIMP1 is an early biomarker for detection and prognosis of lung cancer |
title | TIMP1 is an early biomarker for detection and prognosis of lung cancer |
title_full | TIMP1 is an early biomarker for detection and prognosis of lung cancer |
title_fullStr | TIMP1 is an early biomarker for detection and prognosis of lung cancer |
title_full_unstemmed | TIMP1 is an early biomarker for detection and prognosis of lung cancer |
title_short | TIMP1 is an early biomarker for detection and prognosis of lung cancer |
title_sort | timp1 is an early biomarker for detection and prognosis of lung cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533479/ https://www.ncbi.nlm.nih.gov/pubmed/37759102 http://dx.doi.org/10.1002/ctm2.1391 |
work_keys_str_mv | AT dantasezequiel timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT murthyanirudh timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT ahmedtanvir timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT ahmedmujmmail timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT ramsamoojshakti timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT hurdmauricea timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT lamtiffany timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT malbarimurtaza timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT agrusachristopher timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT elementoolivier timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT zhangchen timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT pappindarrylj timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT mcgrawtimothye timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT stilesbrendonm timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT altorkinasserk timp1isanearlybiomarkerfordetectionandprognosisoflungcancer AT goncalvesmarcusd timp1isanearlybiomarkerfordetectionandprognosisoflungcancer |