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 (October 2023) TIMP1 is an early biomarker for detection and prognosis of lung cancer. Clinical and Translational Medicine, 13 (10). e1391. ISSN 2001-1326

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Abstract

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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders Investigative techniques and equipment diseases & disorders > neoplasms organism description > animal Investigative techniques and equipment > biomarker diseases & disorders > cancer > drugs and therapies diseases & disorders > cancer > cancer types > lung cancer organism description > animal > mammal organism description > animal > mammal > rodent > mouse diseases & disorders > cancer > prognosis organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types
CSHL Authors:	Pappin, Darryl J.
Communities:	CSHL labs > Pappin lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	October 2023
Date Deposited:	10 Oct 2023 15:14
Last Modified:	08 Jan 2024 18:55
PMCID:	PMC10533479
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41170

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