Autotaxin is a novel molecular identifier of type I endometrial cancer

Abstract

Endometrial cancer is the most common cancer of the female genital tract in Western Countries, with an incidence of 150.000 new cases/year. Despite high incidence, little is known about the molecular pathogenesis of this tumor. Phospholipids including lysophosphatidic acid (LPA) are involved in proliferation and dissemination of cancer. LPA is a potent bioactive phospholipid synthesized by autotaxin (ATX) through its lysophospholipase D activity. Recent evidence suggests that the ATX/LPA signaling axis plays a role in endometrial cancer. We carried out a prospective study involving two groups of patients classified in accordance to hysteroscopic-guided biopsy. Patients with histological diagnosis of endometrial cancer were enrolled into group one, whereas control patients with pelvic organ prolapse were assigned group two. Both groups underwent hysterectomy, with either open or laparoscopic surgery. After uterine extraction, a second endometrial biopsy was performed to collect tissues. Real-Time PCR was performed to evaluate ATX gene expression in collected tissues. Statistical analysis including unpaired two-way or one-way Student's t test and ANOVA was performed. We found ATX gene expression significantly higher in neoplastic endometrium compared with normal tissue (P value = 0.0002). In particular, the expression of ATX was significantly elevated in type I endometrial cancer (i.e., endometrioid histotype) compared to type II, in premenopausal women and in patients affected either by obesity (BMI > 30) or diabetes. We propose ATX as a novel potential biomarker particularly implicated in the pathobiology of type I endometrial cancer. Also, we propose ATX as a useful theranostic target in endometrial cancer.

Keywords: Autotaxin (ATX); Biological marker; Endometrial cancer; Lysophosphatidic acid (LPA); Obesity.