Association of MDM2 expression with shorter progression-free survival and overall survival in patients with advanced pancreatic cancer treated with gemcitabine-based chemotherapy

Abstract

This study evaluated the prognostic roles of murine double minute 2 (MDM2) and p53 in pancreatic cancer patients treated with gemcitabine-based chemotherapy. A total of 137 advanced or recurrent adenocarcinoma patients who were treated with gemcitabine-based palliative chemotherapy were reviewed, selected from 957 patients with pancreatic malignancy between 2008 and 2013 at our hospital. Immunohistochemical staining for MDM2 and p53 with formalin-fixed, paraffin-embedded tumor tissues was independently reviewed. Nuclear or cytoplasmic expression of MDM2 and p53 was found in tumor cells of 30 (21.9%) and 71 (51.8%) patients, respectively. Patients with MDM2 expression had shorter median overall survival (OS) (3.7 vs 5.8 mo; P = .048) and median progression-free survival (PFS) (1.5 vs 2.5 mo; P < .001); by contrast, p53 expression was not correlated with OS or PFS. In the multivariate analysis, MDM2 expression (hazard ratio = 1.731; P = .025) was an independent and unfavorable prognostic factor of OS. Additionally, MDM2 expression was significantly associated with progressive disease (PD) and death (P = .015) following first-line gemcitabine-based therapy. In advanced pancreatic cancer patients, MDM2 expression is associated with shorter OS and PFS after gemcitabine-based chemotherapy.

Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy

“…4E; gene set enrichment analysis, nominal P = 0.0, FDR < 10 −3 ). The association of MDM2 amplification with worse clinical outcome to chemotherapy has been reported in breast cancer (27) and pancreatic cancer (28). We did not observe significant changes for CCNE1 gene itself or its related pathway.…”

Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: A scoping review

“…The above relation between P53 overexpression and diminished response to gemcitabine was not replicated in a study of 137 patients with advanced PDAC. [53] MDM2, a negative regulator of p53 expression was associated with diminished response to gemcitabine-based regimen (mOS=3.7 versus 5.8 months; p=0.048) [65].…”

Role of p53 family isoforms in enhancing aggressiveness and chemoresistance in pancreatic cancer (Review)

“…Mouse double minute 2 (MDM2), Itch and neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) are ubiquitin ligase proteins that are known to suppress p73 in pancreatic cancer (149,154,155), and hence, their expression exhibits enhanced resistance to GEM therapy (156). Targeting these proteins could enhance GEM sensitivity in pancreatic cancer.…”