Ray Irene, Möller-Levet Carla S, Michael Agnieszka, Butler-Manuel Simon, Chatterjee Jayanta, Tailor Anil, Haagsma Ben, Bagwan Izhar, Meira Lisiane B, Ellis Patricia E
Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
Academic Department of Gynaecological Oncology, Royal Surrey NHS Foundation Trust, Guildford, UK.
Cancer Med. 2025 Jul;14(13):e71007. doi: 10.1002/cam4.71007.
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.
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.
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.
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.
子宫内膜癌是一种与肥胖相关的恶性肿瘤，可能受慢性炎症导致的脂肪细胞因子信号传导影响。本研究探讨脂联素、瘦素、白细胞介素6（IL6）、肿瘤坏死因子（TNF）α及其受体在子宫内膜癌患者中的分子表达模式，以及与淋巴管间隙浸润（LVSI）和其他肿瘤特征的关联。
我们采用定量逆转录聚合酶链反应（qRT-PCR）分析上述生物标志物在子宫内膜癌组织中的mRNA表达水平，并与良性子宫内膜组织对照进行比较。此外，评估了脂肪组织和淋巴结中的表达情况，并分析了生物标志物表达、患者人口统计学特征和肿瘤特征之间的相关性。
通过qRT-PCR分析，与由五个良性子宫内膜对照样本混合而成的校准样本相比，子宫内膜癌组织（n = 39）中脂联素、瘦素、IL6、TNFα及其受体IL-6R和TNFRSF1A/B的表达水平更高。有趣的是，脂联素受体ADIPOR1和ADIPOR2与癌症特征如分级、组织学、LVSI和微囊拉长和破碎（MELF）模式呈相反的相关性。LVSI与IL6R和ADIPOR2等标志物水平升高以及OBR（瘦素受体）和ADIPOR1表达降低有关，表明它们有可能作为诊断LVSI的替代标志物。值得注意的是，LVSI患者的癌性淋巴结中脂联素表达较高，而无LVSI患者则相反。
本研究为脂联素受体在子宫内膜癌中的不同作用以及各种标志物与LVSI的关联提供了新的见解，强调在确定治疗策略时进行组织特异性生物标志物评估的必要性。
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