Chronic inflammation has been closely linked to the development and progression of various cancers. The epithelial–mesenchymal transition (EMT) is a process involving the acquisition of mesenchymal features by carcinoma cells and is an important link between inflammation and cancer development. Inflammatory mediators in the tumour micro-environment, such as cytokines and chemokines, can promote EMT changes in cancer cells. The aim of this systematic review is to analyse the effect of cytokines on EMT in gynaecological cancers and discuss their possible therapeutic implications. A search of the databases CINAHL, Cochrane, Embase, Medline, PubMed, TRIP, and Web of Science was performed using the keywords: “cytokines” AND “epithelial mesenchymal transition OR transformation” AND “gynaecological cancer”. Seventy-one articles reported that various cytokines, such as TGF-β, TNF-α, IL-6, etc., promoted EMT changes in ovarian, cervical, and endometrial cancers. The EMT changes included from epithelial to mesenchymal morphological change, downregulation of the epithelial markers E-cadherin/β-catenin, upregulation of the mesenchymal markers N-cadherin/vimentin/fibronectin, and upregulation of the EMT-transformation factors (EMT-TF) SNAI1/SNAI2/TWIST/ZEB. Cytokine-induced EMT can lead to gynaecological cancer development and metastasis and hence novel therapies targeting the cytokines or their EMT signalling pathways could possibly prevent cancer progression, reduce cancer recurrence, and prevent drug-resistance.

The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF-α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endometrial cancer cells and is associated with a better prognosis. Leptin, visfatin and resistin are linked to the stimulation of endometrial cancer growth, proliferation, invasion and metastasis and are associated with worse prognosis or with a higher grade/stage of endometrial cancer. IL-6, Il-11, IL-31, IL-33, TNF-α, TGF-β1, SDF-1 and CXCR are involved in endometrial cancer cell growth and metastasis or involved in epithelial mesenchymal transformation (EMT) or associated with advanced disease. Adipocytokines have been found to directly impact endometrial cancer cell proliferation, invasion and migration. These molecules and their signalling pathways may be used to determine prognosis and course of the disease and may also be exploited as potential targets for cancer treatment and prevention of progression.

The rising global incidence of uterine cancer is linked to the escalating prevalence of obesity. Obesity results in alterations in adipocytokines and IGFs, driving cancer progression via inflammation, increased cell proliferation, and apoptosis inhibition, although the precise mechanisms are still unclear. This study examined a set of six markers, namely, adiponectin, leptin, IL6, TNFα, IGF1, and IGF2 and compared them between fifty age-matched endometrial cancer patients (study group) and non-cancer patients with benign gynaecological conditions (control group). We also assessed the relationship of these markers with obesity and explored the correlation between these markers and various tumour characteristics. In the cancer population, these markers were also assessed 24 h and 6 months post-surgery. Remarkably, low adiponectin levels were associated with a 35.8% increase in endometrial cancer risk. Interestingly, compared to control subjects where IGF levels decreased after menopause, post-menopausal women in the study group showed elevated IGF1 and IGF2 levels, suggesting a potential influence of endometrial cancer on the IGF system, particularly after menopause. Lastly, it is noteworthy that a discernible inverse relationship trend was observed in the levels of adipocytokines and IGFs 6 months post-surgery. This indicates that treatment for endometrial cancer may have a differential impact on adipocytokines and IGFs, potentially holding clinical significance that merits further investigation.

Background: Endometrial cancer, a malignancy linked with obesity, may be influenced by adipocytokines signalling due to chronic inflammation. This study explores the molecular expression patterns of adiponectin, leptin, interleukin6 (IL6), tumor necrosis factor (TNF)α, and their receptors in endometrial cancer patients and associations with lymphovascular space invasion (LVSI) and other tumour characteristics. Methods: We analysed mRNA expression levels of the above biomarkers in endometrial cancer tissue using quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR), comparing them to benign endometrial tissue controls. Additionally, expressions in adipose tissue and lymph nodes were assessed, with correlations drawn between biomarker expression, patient demographics, and tumor characteristics. Results: Using qRT‐PCR analysis, endometrial cancer tissues ( n = 39) exhibited higher expression levels of adiponectin, leptin, IL6, TNFα, and their receptors, IL6R and TNFRSF1A/B, compared to the calibrator sample, which consisted of five pooled benign endometrial control samples. Intriguingly, the adiponectin receptors, ADIPOR1 and ADIPOR2 demonstrated opposing correlations with cancer characteristics such as grade, histology, LVSI, and microcystic elongated and fragmented (MELF) pattern. LVSI was linked to increased levels of markers such as IL6R and ADIPOR2, along with decreased expressions of OBR (leptin receptor) and ADIPOR1, suggesting their potential as surrogate markers for diagnosing LVSI. Notably, higher adiponectin expression was observed in the cancerous lymph nodes of patients with LVSI, contrasting with those without LVSI. Conclusion: This study provides novel insight into differential role of adiponectin receptors in endometrial cancer and the associations of various markers with LVSI, emphasizing the need for tissue‐specific biomarker assessments in determining treatment strategies.