Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention

Huang, Ting; Zhou, Jingyi; Wang, Jianliu

doi:10.7150/ijbs.68591

Cited by 17 publications

(8 citation statements)

References 149 publications

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“…There were also studies showing that, as an atypical cadherin, FAT2 could exert biological functions through the Hippo pathway, which is closely related to the maintenance of tissue homeostasis and to multiple processes including cancers 36,37 . In our study, patients with FAT2 mutations were identified enriched in the cAMP and calcium signaling pathway, and cAMP and calcium signaling pathways participated in cell proliferation, migration, and metastasis of UCEC 38,39 . Moreover, we investigated the expression differences of various immune cells between FAT2 mutation and wild‐type tumor tissues.…”

Section: Discussionmentioning

confidence: 80%

“… 36 , 37 In our study, patients with FAT2 mutations were identified enriched in the cAMP and calcium signaling pathway, and cAMP and calcium signaling pathways participated in cell proliferation, migration, and metastasis of UCEC. 38 , 39 Moreover, we investigated the expression differences of various immune cells between FAT2 mutation and wild‐type tumor tissues. We found higher expression of activated CD4/CD8 T cells and plasmacytoid dendritic cells in FAT2 mutation patients.…”

Section: Discussionmentioning

confidence: 99%

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FAT2 mutation is associated with better prognosis and responsiveness to immunotherapy in uterine corpus endometrial carcinoma

et al. 2022

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Background Uterine corpus endometrial carcinoma (UCEC) ranks sixth among malignant tumors in women and the mortality is still rising. FAT2 gene has been considered to be related to the survival and prognosis of some certain diseases in previous studies, but the FAT2 mutation status in UCEC and its prognostic value has been rarely studied. Hence, the purpose of our study was to explore the role of FAT2 mutations for predicting prognosis and responsiveness to immunotherapy in patients with UCEC. Methods UCEC samples from the Cancer Genome Atlas database were analyzed. We evaluated the impact of FAT2 gene mutation status and clinicopathological characteristics on the prognosis of UCEC patients and used univariate and multivariate Cox analysis risk scores to independently predict patient overall survival (OS). Tumor mutation burden (TMB) values of the FAT2 mutant and non‐mutant groups were computed by Wilcoxon rank sum test. The correlation of FAT2 mutation and half maximal inhibitory concentration (IC50) values of various anticancer drugs was analyzed. Gene Ontology data and Gene Set Enrichment Analysis (GSEA) were employed to examine the differential expression of genes between the two groups. Finally, a single‐sample GSEA arithmetic was utilized to measure the abundance of tumor‐infiltrating immune cells in UCEC patients. Results FAT2 mutations suggested better OS ( p < 0.001) and disease‐free survival (DFS) ( p = 0.007) in UCEC. The IC50 values of 18 anticancer drugs were upregulated in FAT2 mutation patients ( p < 0.05). The TMB and microsatellite instability values of patients with FAT2 mutations were significantly higher ( p < 0.001). Next, the Kyoto Encyclopedia of Genes and Genomes functional analysis and GSEA revealed the potential mechanism of FAT2 mutation on the tumorigenesis and progression of UCEC. In addition, in reference to the UCEC microenvironment, the infiltration levels of activated CD4/CD8 T cells ( p < 0.001/ p = 0.001) and plasmacytoid dendritic cells ( p = 0.006) were upregulated in the non‐FAT2 mutation group, and Type 2 T helper cells ( p = 0.001) were downregulated in the FAT2 mutation group. Conclusions UCEC patients with FAT2 mutations have better prognosis and are more likely to respond to immunotherapy. FAT2 mutation may be a valuable predictor for prognosis and responsiveness to immunotherapy in UCEC patients.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

FAT2 mutation is associated with better prognosis and responsiveness to immunotherapy in uterine corpus endometrial carcinoma

et al. 2022

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“…It has been reported that abnormal changes in amplitude of cytoplasmic free Ca 2+ concentration and duration of Ca 2+ elevation may promote breast cancer cell proliferation and invasion [17,21]. Te same phenomenon was confrmed in endometrial and colorectal cancers [22,23].…”

Section: Introductionmentioning

confidence: 72%

Role of SERCA3 in the Prognosis and Immune Function in Pan-Cancer

Li²,

Huang

et al. 2022

Journal of Oncology

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The sarcoendoplasmic reticulum calcium adenosine triphosphatase (ATPase) 3 (SERCA3), a member of the SERCA protein family, is located at the endoplasmic reticulum. Its main function is to pump Ca2+ into the endoplasmic reticulum and is involved in maintaining intracellular calcium homeostasis and signal transduction, which are very important factors impacting cancer development and progression. However, the specific role of SERCA3 in cancer remains unclear. Our study, for the first time, comprehensively analyzed the SERCA3 expression profile in multiple cancers and its prognostic value in different cancers using bioinformatics. Furthermore, TCGA database was applied to evaluate the certain correlation of SERCA3 expression with immune modulator genes, immune checkpoints, immune cell infiltration, TMB, and MSI. The results revealed that in many cancers, SERCA3 expression was markedly decreased, which was related to poor prognosis. Additionally, we noticed that SERCA3 expression was correlated with TNM classification and WHO cancer stages in some cancer types. The Pearson correlation analysis showed that SERCA3 expression was closely associated with chemokines, chemokine receptors, MHC, immune activation genes, and immunosuppressive genes. In most cancer types, SERCA3 expression was also associated with immune checkpoints, including PDCD1 and CTLA-4. Further analysis suggested that SERCA3 was significantly correlated with CD8+ T cells, and regulatory T cells. Additionally, pan-cancer analysis confirmed that SERCA3 expression was related to TMB and MSI. In conclusion, these results offer a new insight into the functions and effects of SERCA3 in pan-cancer, and further provide some basis for considering SERCA3 as a potential cancer treatment target and biomarker.

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“…Cows also had greater protein expression/cell of AHR and a tendency for greater CYP1A2 mRNA, a target of AHR activation. AHR expression can be induced by IL6 signaling and AHR activation can upregulate transcription and synthesis of IL6 (Stobbe-Maicherski et al, 2013; Huang et al, 2022). Interestingly, AHR activation is involved with wasting syndrome (Girer et al, 2021) and obesity related fatty liver and inflammation (Pohjanvirta, 2017; Bock, 2021) and participates in leukocyte energy metabolism, neutrophil chemotaxis, and bacterial clearance (Partida-Sánchez et al, 2001; Bunaciu et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effects of parity and early pregnancy on peripheral blood leukocytes in dairy cattle

da Silva,

Oli,

Gambonini

et al. 2024

Preprint

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Subfertility remains a major problem in the dairy industry. Only 35-40% of high-yielding dairy cows and 55-65% of nonlactating heifers become pregnant after their first service. The immune system plays a critical role in the establishment of pregnancy. However, it can also create challenges for embryo survival and contribute to reduced fertility. We conducted 2 separate experiments to characterize changes in subsets of peripheral blood leukocytes (PBL) and their phenotype over the estrous cycle and early pregnancy in heifers and cows. We used flow cytometry and RT-qPCR to assess protein and mRNA expression of molecules important for immune function. We observed that monocytes and T cells were most affected by pregnancy status in heifers, whereas, CD8+ lymphocytes and natural killer (NK) cells were most affected during early pregnancy in cows. Changes in immune parameters measured appeared to be greater in heifers than cows including changes in expression of numerous immune function molecules. To test the hypothesis, we conducted a third experiment to simultaneously analyze the immunological responses to pregnancy between cows and heifers. We observed that cows had greater expression of proinflammatory cytokines and molecules associated with leukocyte migration and phagocytosis compared to heifers. Moreover, animals that failed to become pregnant showed altered expression of anti-inflammatory molecules. Overall, these findings support the hypothesis that early pregnancy signaling alters the proportions and functions of peripheral blood immune cells and differences between cows and heifers may yield insight into the reduced fertility of mature lactating dairy cows.

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Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention

Cited by 17 publications

References 149 publications

FAT2 mutation is associated with better prognosis and responsiveness to immunotherapy in uterine corpus endometrial carcinoma

FAT2 mutation is associated with better prognosis and responsiveness to immunotherapy in uterine corpus endometrial carcinoma

Role of SERCA3 in the Prognosis and Immune Function in Pan-Cancer

Effects of parity and early pregnancy on peripheral blood leukocytes in dairy cattle

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