Molecular cues on obesity signals, tumor markers and endometrial cancer

Abstract

Tumor markers are important tools for early diagnosis, prognosis, therapy response and endometrial cancer monitoring. A large number of molecular and pathologic markers have been described in types I and II endometrial cancers, which has served to define the main oncogenic, epidemiological, genetic, clinical and histopathological features. Ongoing attempts to stratify biological markers of endometrial cancer are presented. However, data on changes in tumor marker profiles in obesity-related endometrial cancer are scarce. Obesity is a pandemic in Western countries that has an important impact on endometrial cancers, albeit through not very well-defined mechanisms. Although endometrial cancer is more common in Caucasian women, higher mortality is found in African Americans who also show higher incidence of obesity. Here, we describe how obesity signals (estrogen, leptin, leptin induced-molecules, Notch; cytokines and growth factors) could affect endometrial cancer. Leptin signaling and its crosstalk may be associated to the more aggressive and poor prognosis type II endometrial cancer, which affects more postmenopausal and African-American women. In this regard, studies on expression of novel molecular markers (Notch, interleukin-1 and leptin crosstalk outcome) may provide essential clues for detection, prevention, treatment and prognosis.

Leptin signaling and cancer chemoresistance: Perspectives

“…In breast and pancreatic cancer cells leptin upregulates Notch receptors, ligands and targets[16,60]. Moreover, latest reports show a positive correlation between leptin, Ob-R and Notch components in endometrial cancer tissues from obese patients[70]. Leptin induces RBP-Jk and Notch that impacts on CSC and self-renewal[16,60,71].…”

Pancreatic Cancer and Obesity: Some Molecular Perspectives

“…Leptin-Notch crosstalk likely plays a role in these cancers [30][31][32], where it also enhances angiogenic transformation of endothelial cells [33]. Notch, IL-1 and leptin are known factors involved in PC growth, progression, and chemoresistance.…”

Emerging Biomarkers and Clinical Implications in Endometrial Carcinoma

“…EmCa is a malignancy of the endometrial glands of the uterus and is the most frequent malignancy of the female pelvic reproductive tract [12]. EmCa comprises a series of malignant diseases of the endometrium with diverse phenotypes.…”

“…Although it is not categorical, EmCa can be subdivided into two main different types based on the histologic examination: endometrioid and non-endometrioid with their variants [12]. EmCa may also be classified based on epidemiological, histologic, and behavioral information into two types: Type I EmCa and Type II EmCa (Figure 2) [12]. Type I EmCa comprising the endometrioid carcinomas is the most common type of adenocarcinoma.…”

“…Type I EmCa comprising the endometrioid carcinomas is the most common type of adenocarcinoma. Then, Type I accounts for 85% of all EmCa cases and is more common than Type II EmCa (non-endometrioid carcinoma) [12]. Type I EmCa is dependent on estrogen hormonal stimulation, less aggressive, and shows a favorable prog-nosis [12,13].…”