Alonso-Alconada Lorena, Santacana Maria, Garcia-Sanz Pablo, Muinelo-Romay Laura, Colas Eva, Mirantes Cristina, Monge Marta, Cueva Juan, Oliva Esther, Soslow Robert A, Lopez Maria Angeles, Palacios Jose, Prat Jaime, Valls Joan, Krakstad Camilla, Salvesen Helga, Gil-Moreno Antonio, Lopez-Lopez Rafael, Dolcet Xavier, Moreno-Bueno Gema, Reventos Jaume, Matias-Guiu Xavier, Abal Miguel
Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Fundacion Ramon Dominguez, SERGAS, Santiago de Compostela, Spain.
Int J Cancer. 2015 Apr 15;136(8):1863-73. doi: 10.1002/ijc.29213. Epub 2014 Sep 29.
Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine-confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy.
子宫内膜癌是女性生殖道最常见的恶性肿瘤，通常在疾病局限于子宫的早期阶段被诊断出来，总体预后良好。然而，高达20%的子宫内膜癌最终会复发，这与生存率下降相关，是主要的临床挑战。对这组高危患者的管理依赖于强大的生物标志物，这些标志物可以预测哪些子宫内膜癌会复发。为此，我们进行了一项蛋白质组学分析，比较原发性病变和复发病变，并将膜联蛋白A2（ANXA2）鉴定为与复发性疾病相关的潜在生物标志物，我们通过免疫组化在另一组独立样本中进一步验证了这一结果。我们在体外证明ANXA2在促进转移方面发挥作用，而不是干扰对放疗/化疗的敏感性。此外，在子宫内膜癌播散的小鼠模型中，沉默ANXA2导致转移模式减少，循环肿瘤细胞数量有限。最后，对93名患者的队列进行的一项回顾性研究表明，ANXA2有效地预测了最终复发的子宫内膜样子宫内膜癌。重要的是，ANXA2在低风险的I期子宫内膜样子宫内膜癌中也显示出预测价值，突出了ANXA2生物标志物作为子宫内膜癌复发疾病预测指标的临床实用性。正在进行回顾性和前瞻性研究，以验证ANXA2作为一种潜在工具，用于对可能接受根治性手术和放疗/化疗的患者进行最佳分层。
