Serum calcium is a novel parameter to assess metabolic syndrome in endometrial carcinoma

Lin, Yanying; Zhou, Jingyi; Cao, Linlin; Xu, Qi; Hao, Juan; Zhao, Lijun; Wang, Jianliu

doi:10.3802/jgo.2019.30.e12

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Previously in our study, we demonstrated that in EC patients, serum calcium might be a more sensitive parameter for metabolic syndrome, which is a well-established risk factor for EC. 18 Another formation of metastatic tumor cells, positive peritoneal cytology, had a strong correlation with elevated ionized calcium level, indicating that calcium might have an effect on metastatic ability of EC cells. 19 It was reported that up-regulated calcium level might lead to the metabolic syndrome through Ca 2+ /cAMP signaling pathway.…”

Section: Discussionmentioning

confidence: 93%

<p>Increased Serum Calcium Level Promotes the Risk of Lymph Node Metastasis in Endometrial Cancer</p>

Dong

Cheng

et al. 2020

CMAR

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The early predictive values of diagnostic markers for lymph node metastasis (LNM) in endometrial cancer (EC) are still unclear at present. The purpose of this study is to explore the relationship between serum calcium and LNM in EC. Methods: We identified all patients with EC who underwent surgery between January 2012 and December 2016. Patient characteristics and various preoperative clinicopathologic data were obtained from medical records and were reviewed retrospectively. These patients were divided into two groups according to the pathology of their lymph node. Logistic regression models analyzed the relationship between the ionized calcium and LNM of EC patients, while adjusting for the potential confounders. Results: A total of 448 patients were assessed. Univariate analysis showed that ionized calcium, CA125 level, tumor grade, peritoneal cytology, FIGO stage, histological type, LVSI, and myometrial invasion were positively correlated with LNM (all P<0.05). The risk of LNM increased with the promotion of serum ionized calcium (P for trend <0.01). Ionized calcium level was significant before and after the adjustment of cofounders (unadjusted: OR=11.9, 95% CI: 4.8-29.6, P< 0.01; model I: OR=11.3, 95% CI: 4.5-28.8, P< 0.01; model II: OR=5.2, 95% CI: 1.6-17.2, P< 0.05). Additionally, the risk of ionized calcium was especially evident in patients whose age was older than 60, BMI<28 kg/m 2 , grade 3, negative peritoneal cytology and endometrioid endometrial adenocarcinoma. Conclusion: Ionized calcium level was highly associated with LNM in EC and acted as a potential biomarker in predicting the risk of LNM in EC.

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Section: Discussionmentioning

confidence: 93%

<p>Increased Serum Calcium Level Promotes the Risk of Lymph Node Metastasis in Endometrial Cancer</p>

Dong

Cheng

et al. 2020

CMAR

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“…Despite different studies, new molecular markers have been reported, but to date, no reliable molecular markers have been applied to clinical molecular typing. Our recent study found that serum total calcium may be a more sensitive metabolic syndrome parameter than hyperlipidemia in patients with endometrioid cancer (130).…”

Section: Resultsmentioning

confidence: 99%

The Role of Metabolic Syndrome in Endometrial Cancer: A Review

2019

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Endometrial cancer is one of the most common cancers of the female reproductive system. Although surgery, radiotherapy, chemotherapy, and hormone therapy can significantly improve the survival of patients, the treatment of patients with very early lesions and a strong desire to retain reproductive function or late recurrence is still in the early stages. Metabolic syndrome (MS) is a clustering of at least three of the five following medical conditions: central obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Obesity, diabetes and hypertension often coexist in patients with endometrial cancer, which increases the risk of endometrial cancer, also known as the “triple syndrome of endometrial cancer.” In recent years, epidemiological and clinical studies have found that MS associated with metabolic diseases is closely related to the incidence of endometrial cancer. However, the key molecular mechanisms underlying the induction of endometrial cancer by MS have not been elucidated to date. Characterizing the tumor metabolism microenvironment will be advantageous for achieving a comprehensive view of the molecular mechanism of metabolic syndrome associated with endometrial cancer and for providing a new target for the treatment of endometrial cancer. This review focuses on recent advances in determining the role of metabolic syndrome-related factors and mechanisms in the pathogenesis of endometrial cancer. We suggest that interfering with the tumor metabolic microenvironment-related molecular signals may inhibit the occurrence of endometrial cancer.

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“…Calcium ions increased the expression of TRPV4 by VPAC1, CaSR, and Ca 2+ -activated K + channels including SK1/3, IK1, and BK in other cancers, but the mechanism of overexpressed TRPV4 in EC still remained elusive 11 , 35 , 38 . As a potent intracellular second messenger, the elevation of serum calcium might be associated with metabolic syndrome in EC 39 , and increased calcium influx promoted the stiffness of tissue 40 . Moreover, TRPV4 was a mechanosensitive channel, and the expression of TRPV4 was regulated by tissue stiffness 32 , 41 .…”

Section: Discussionmentioning

confidence: 99%

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer

Cheng

Wang

et al. 2020

Cell Death Dis

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Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel that has been associated with several types of cancer. However, its biological significance, as well as its related mechanism in endometrial cancer (EC) still remains elusive. In this study, we examined the function of calcium in EC, with a specific focus on TRPV4 and its downstream pathway. We reported here on the findings that a high level of serum ionized calcium was significantly correlated with advanced EC progression, and among all the calcium channels, TRPV4 played an essential role, with high levels of TRPV4 expression associated with cancer progression both in vitro and in vivo. Proteomic and bioinformatics analysis revealed that TRPV4 was involved in cytoskeleton regulation and Rho protein pathway, which regulated EC cell migration. Mechanistic investigation demonstrated that TRPV4 and calcium influx acted on the cytoskeleton via the RhoA/ROCK1 pathway, ending with LIMK/cofilin activation, which had an impact on F-actin and paxillin (PXN) levels. Overall, our findings indicated that ionized serum calcium level was significantly associated with poor outcomes and calcium channel TRPV4 should be targeted to improve therapeutic and preventive strategies in EC.

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Serum calcium is a novel parameter to assess metabolic syndrome in endometrial carcinoma

Cited by 14 publications

References 24 publications

<p>Increased Serum Calcium Level Promotes the Risk of Lymph Node Metastasis in Endometrial Cancer</p>

<p>Increased Serum Calcium Level Promotes the Risk of Lymph Node Metastasis in Endometrial Cancer</p>

The Role of Metabolic Syndrome in Endometrial Cancer: A Review

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer

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