Identification of two theranostic biomarker panels for epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is the most common form of ovarian cancer (OC), which is the second leading cause of death among gynecologic cancers in women worldwide (gco.iarc.fr). In Tunisia, the incidence of OC is 3.6 /100,000 and accounts for 1.6% of all cancer-related deaths in women (gco.iarc.frwww.gco.iarc.fr). EOC is often referred to as a 'silent killer' because most cases remain undetected until the late stages, and the cancer spreads and metastasizes to the abdomen without obvious or sensitive symptoms [1]. Despite its high morbidity, there are only two screening tests for EOC to date. The first is serological screening of CA-125 level, which is elevated in more than 80% of OC patients. However, this carcinogen is also elevated in 1% of healthy women [2]. It has also been shown that CA-125 serum only has a sensitivity of 50-60% for early stage and thus is not sufficient for early EOC screening or diagnosis [2]. The second test is imaging by transvaginal sonography alone or in combination with Doppler, which is sensitive and specific only for established tumors [3] Additional approaches are needed to enable high-throughput screening with high specificity and sensitivity for EOC.

Along with other factors such as heredity, environment, and lifestyle, inflammation emerges as an important risk factor for EOC [1]. During a woman's lifetime, the repeated secretion of cytokines, chemokines, and other growth factors by the ovaries and immune cells creates a chronic inflammatory microenvironment, which in turn promotes the conversion of normal cells into malignant cells, supporting tumor progression, metastatic development, and resistance to chemotherapy (CT) [1]. Recent studies have investigated the deregulation of a panel of proteins at serum levels in patients with various cancers, including EOC, to identify a set of specific analytes that can be used as theranostic biomarkers for each tumour disease [4], [5]. Yurkuvesky et al. have investigate ninety-six serum biomarkers in sera from healthy women and from patients with ovarian cancer, benign pelvic tumours, and breast, colorectal, and lung cancers using multiplex xMAP bead-based immunoassays and found that a selective panel providing the highest diagnostic performance of 86% sensitivity (SN) for early-stage OC and 93% SN for late-stage OC at 98% specificity (SP) consisted of CA-125, HE4, CEA, and VCAM-1. However, all these studies that investigated molecular panels using a multiplex technology focused on the diagnostic side of the biomarkers without mentioning their theranostic effect [4]

In this context, we analysed, using the ProcartaPlex technology, 65 serum proteins that essentially act as immune mediators, including 33 cytokines, 18 chemokines, 6 growth factors/regulators, and 8 soluble receptors, to identify a panel of theranostic biomarkers for EOC.

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