ArticleThe Journal of experimental medicine2021
TIMP1 expression underlies sex disparity in liver metastasis and survival in pancreatic cancer.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Serum TIMP-1 shows a potential association with metastatic disease in patients with pancreatic cancer: a pilot analysis without a healthy control cohort.Clinical and experimental medicine · 2026Article
- Serum TIMP-1 concentrations are associated with cancer incidence and cancer-related mortality in a population-based cohort.Scientific reports · 2026Article
- <p>Unveiling sex differences in pancreatic ductal adenocarcinoma: Current evidence and future directions (Review)</p>.International journal of oncology · 2026Review
- Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.Cell reports. Medicine · 2026Article
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Integrin-Mediated TIMP1 Signaling Reprograms Liver Macrophages and Accelerates Colorectal Cancer Metastasis.Cells · 2025Article
- Comprehensive Analysis of scRNA-Seq and Bulk RNA-Seq Identified TIMP1 as a Prognostic Marker in Colorectal Cancer.Immune network · 2025Article
- Article
- Real-World Validation of the Purity Independent Subtyping of Tumors Classifier for Informing Therapy Selection in Pancreatic Ductal Adenocarcinoma.JCO precision oncology · 2025Article
- The Role of the TIMP1/LINC01615 Axis as a Regulator of the EMT Pathway in Gastric Cancer.Biological procedures online · 2025Article
- Serum proteomics reveals survival-associated biomarkers in pancreatic cancer patients treated with chemoimmunotherapy.iScience · 2025Article
- Putative function and prognostic molecular marker of mast cells in colorectal cancer.BMC medical genomics · 2025Article
- Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.Molecular cancer · 2025Article
- Bioinformatics and experimental unveiling of TIMP1 as a novel therapeutic target in colorectal cancer ferroptosis.Frontiers in oncology · 2025Article
- Sex-Related Differences in Pancreatic Ductal Adenocarcinoma Progression and Response to Therapy.International journal of molecular sciences · 2024Review
- Combined Analysis of Second- and Third-Generation Transcriptome Sequencing for Gene Characteristics and Identification of Key Splicing Variants in Wound Healing of Ganxi Goat Skin.Animals : an open access journal from MDPI · 2024Article
- Article
- The impact of sex on metastasis.Nature reviews. Cancer · 2024Article
- Evidence-Based Severity Assessment of Animal Models for Pancreatic Cancer.Biomedicines · 2024Article
- Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.The Journal of clinical endocrinology and metabolism · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sex disparity in cancer is so far inadequately considered, and components of its basis are rather unknown. We reveal that male versus female pancreatic cancer (PC) patients and mice show shortened survival, more frequent liver metastasis, and elevated hepatic metastasis-promoting gene expression. Tissue inhibitor of metalloproteinases 1 (TIMP1) was the secreted factor with the strongest male-biased expression in patient-derived pancreatic tumors. Male-specific up-regulation of systemic TIMP1 was demonstrated in PC mouse models and patients. Using TIMP1-competent and TIMP1-deficient PC mouse models, we established a causal role of TIMP1 in determining shortened survival and increased liver metastasis in males. Observing TIMP1 expression as a risk parameter in males led to identification of a subpopulation exhibiting increased TIMP1 levels (T1HI males) in both primary tumors and blood. T1HI males showed increased risk for liver metastasis development not only in PC but also in colorectal cancer and melanoma. This study reveals a lifestyle-independent sex disparity in liver metastasis and may open new avenues toward precision medicine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.