Activity and clinical relevance of autotaxin and lysophosphatidic acid pathways in high-grade serous carcinoma.

Abstract

The aim of this study was to analyze the expression, biological role and clinical relevance of autotaxin (ATX), the enzyme synthetizing lysophosphatidic acid (LPA), and LPA receptors (LPAR) in high-grade serous carcinoma (HGSC). mRNA expression by qRT-PCR of LPAR1-6 was analyzed in 155 HGSC specimens (88 effusions, 67 solid lesions). ATX mRNA expression was analyzed in 97 specimens. ATX, ERK, and AKT protein expression was studied by Western blotting. LPAR2 mRNA was overexpressed in HGSC cells in effusions compared to solid lesions, with opposite findings for LPAR3 and LPAR6 mRNA and ATX protein. Higher LPAR1 levels were significantly related to longer overall survival (OS) in pre-chemotherapy effusions (p = 0.027). Conversely, higher expression of LPAR1, LPAR2, and LPAR5 in post-chemotherapy effusions was significantly associated with shorter OS (p = 0.037, p = 0.025 and p = 0.021, respectively) and progression-free survival (PFS) (p < 0.001, p = 0.007 and p < 0.001, respectively) in univariate survival analysis. LPAR1 mRNA expression was an independent prognosticator of OS in patients with pre-chemotherapy effusions and PFS in patients with post-chemotherapy effusions (p = 0.013 both). In conclusion, LPAR mRNA and ATX protein levels are anatomic site-dependent in HGSC and the former are informative of disease outcome.

• Authors: Hadil Onallah, Liora Jacobs Catane, Claes G Tropé, Thea E Hetland Falkenthal, Reuven Reich, Ben Davidson
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 473 Issue 4 Pg. 463-470 (Oct 2018) ISSN: 1432-2307 [Electronic] Germany
• PMID: 30032361 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Lysophospholipids
• RNA, Messenger
• Receptors, Lysophosphatidic Acid
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Phosphoric Diester Hydrolases
• alkylglycerophosphoethanolamine phosphodiesterase
• lysophosphatidic acid

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma (enzymology, genetics, secondary, therapy)
• Disease-Free Survival
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Kaplan-Meier Estimate
• Lysophospholipids (metabolism)
• Middle Aged
• Multivariate Analysis
• Neoplasm Grading
• Neoplasm Staging
• Neoplasms, Cystic, Mucinous, and Serous (enzymology, genetics, secondary, therapy)
• Ovarian Neoplasms (enzymology, genetics, pathology, therapy)
• Phosphoric Diester Hydrolases (genetics, metabolism)
• Phosphorylation
• Proportional Hazards Models
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (genetics)
• Receptors, Lysophosphatidic Acid (genetics, metabolism)
• Risk Factors
• Signal Transduction
• Time Factors
• Treatment Outcome