Purpose: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the proliferation and survival of several cancer cell types. However, little is known about the prognostic role of PGRN in advanced biliary tract cancers (BTCs).
Methods: A retrospective analysis was performed on patients with advanced BTC who received palliative chemotherapy between July 2004 and November 2014. PGRN expression was immunohistochemically evaluated according to staining intensity of tumor and peritumoral cells.
Results: A total of 80 patients (39 intrahepatic, 26 extrahepatic, and 18 gallbladder tumors) were analyzed. The median age was 64 years (range 31-79), and 48 patients (60 %) were male. Thirty-five patients (44 %) had high tumor PGRN expression (PGRN positive), and there was a trend of poorer response to chemotherapy in patients with PGRN-positive tumor in terms of overall response rate (7 vs. 18 %). With a median follow-up duration of 17.7 months (range 4.9-35.1), PGRN-positive patients had worse progression-free survival (PFS) with a median of 2.7 months compared to 5.0 months for PGRN-negative patients (P = 0.023). After adjusting for possible confounding factors including sex, age, performance status, disease status, and chemotherapy agent, multivariate analysis showed that PGRN-positive tumor was a prognostic factor independently associated with poor PFS (hazard ratio 1.69, 95 % CI 1.02-2.81; P = 0.044).
Conclusion: PGRN overexpression was significantly associated with poor PFS in advanced BTCs. PGRN expression by IHC analysis might help predict treatment outcomes and provide a new target for molecular therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00280-016-3170-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy in transgenic Caenorhabditis elegans.
Alzheimers Dement
December 2024
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA.
Introduction: Genetic variation in the lysosomal and transmembrane protein 106B (TMEM106B) modifies risk for several neurodegenerative disorders, especially frontotemporal lobar degeneration (FTLD). The C-terminal (CT) domain of TMEM106B occurs as fibrillar protein deposits in the brains of dementia patients.
Methods: To determine the TMEM CT aggregation propensity and neurodegenerative potential, we generated transgenic Caenorhabditis elegans expressing the human TMEM CT fragment aggregating in FTLD cases.
PGRN protects against serum deprivation-induced cell death by promoting the ROS scavenger system in cervical cancer.
Cell Death Dis
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.
Progranulin (PGRN), an autocrine growth factor with tumorigenic roles in a variety of tumors, is a putative survival factor for normal and cancer cells in vitro. However, the fundamental mechanism of PGRN-mediated survival of cancer cells suffering from various types of microenvironmental stresses, such as serum deprivation, remains unknown. We show here that serum deprivation decreases intracellular PGRN protein levels in cervical cancer cells.
View Article and Find Full Text PDFBioinformatics- and quantitative proteomics-based identification of gastric adenocarcinoma-related proteins and analysis.
Am J Cancer Res
November 2024
Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, Hebei, China.
Background: The emergence of immune resistance and a lack of effective therapeutic targets have become significant challenges in immunotherapy, highlighting the urgent need for new molecular markers and treatment targets. Moreover, the significance and mechanisms of PGRN (Progranulin) in gastric cancer remain ambiguous.
Objective: To identify differentially expressed proteins in gastric cancer and elucidate the function and mechanism of PGRN.
O-GlcNAcylation of progranulin promotes hepatocellular carcinoma proliferation.
Biochem Biophys Res Commun
January 2025
Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Dongguan, 523000, China. Electronic address:
Progranulin (PGRN) is overexpressed and implicated in hepatocellular carcinoma (HCC) development; however, its post-translational modifications and regulatory mechanisms in HCC remain largely unexplored. Here, the expression levels of PGRN, OGT, and O-GlcNAcylation were found to be elevated in both HCC samples and cell lines. LC-MS/MS analysis and immunoprecipitation revealed that PGRN underwent O-linked N-acetylglucosamine (O-GlcNAc) modification at threonine 272 (Thr272).
View Article and Find Full Text PDFGranulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.
Cell Rep
December 2024
Department of Pharmacology and Chemical Biology, Emory University, School of Medicine, Atlanta, GA 30322, USA; Center for Neurodegenerative Disease, Emory University, School of Medicine, Atlanta, GA 30322, USA; Department of Neurology, Emory University, School of Medicine, Atlanta, GA 30322, USA. Electronic address:
Progranulin (PGRN) deficiency is linked to neurodegenerative diseases, including frontotemporal dementia (FTD), Alzheimer's disease, and Parkinson's disease. Proper PGRN levels are critical for brain health; however, the function of PGRN is unclear. PGRN is composed of 7.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!