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分析癌症复发的驱动因素:激素依赖性女性癌症中的低钙血症与铁吸收

Analyzing the drivers of cancer relapse: hypocalcemia and iron absorption in hormone-dependent female cancers.

作者信息

Chittineedi Prasanthi, Pandrangi Santhi Latha, Bellala Ravi Shankar, Sánchez Llaguno Sungey Naynee, Mohiddin Gooty Jaffer, Neira Mosquera Juan Alejandro, Bellala Venkata Madhavi, Kolli Viswa Kalyan

机构信息

Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, School of Science, GITAM (Deemed to be) University Visakhapatnam 530045, India.

Department of Clinical Oncology, Omega Hospitals Visakhapatnam, India.

出版信息

Am J Transl Res. 2022 Sep 15;14(9):6563-6573. eCollection 2022.

Abstract

BACKGROUND

Alterations in the levels of nutrients like calcium, ferritin, and electrolytes play a pivotal role in human physiology and might serve as biomarkers. Ferritin, an iron storage protein is important in various metabolic reactions of both cancer and cancer stem cells (CSCs) and is found to regulate 'stemness' leading to cancer relapse. Interestingly, ferritin levels are found to be regulated by calcium uptake. Several studies have shown that high levels of calcium inhibit absorption of iron, thereby reducing ferritin levels. In the present study, we evaluated and correlated the serum ferritin and calcium levels in pre- and post-treated hormone-dependent female cancers and deciphered their role in tumor recurrence and relapse.

MATERIALS AND METHODS

The present retrospective study was approved by the Institutional Ethical Committees (IEC) of GIMSR (No. GIMSR/Admn./Ethics/approval/IEC-3/2021), and Omega cancer hospitals (Reg No: ECR/1486/Inst/AP/2020). Serum from 197 clinical samples diagnosed with breast, cervical, and ovarian cancers (99 pre-and 98 post-treatment) and 10 blood samples were analyzed for ferritin and calcium using auto bioanalyzer and sandwich enzyme-linked immunosorbent assay (ELISA).

RESULTS

Ferritin levels were elevated in both pre- and post-treatment hormone-dependent female cancer patients while calcium levels showed gradual decrease. The mean ferritin value for pre-treatment was 0.0409 mg/dL while it was 0.0428 mg/dL for post-treatment hormone-dependent female cancer.

CONCLUSION

Our results suggest that hypocalcaemia in post-treatment cancer patients leads to ferritin accumulation which might make these patients more prone to tumor recurrence and relapse.

摘要

背景

钙、铁蛋白和电解质等营养物质水平的改变在人体生理过程中起关键作用,可能作为生物标志物。铁蛋白是一种铁储存蛋白,在癌症和癌症干细胞(CSCs)的各种代谢反应中都很重要,并且发现它能调节导致癌症复发的“干性”。有趣的是,发现铁蛋白水平受钙摄取的调节。多项研究表明,高水平的钙会抑制铁的吸收,从而降低铁蛋白水平。在本研究中,我们评估并关联了激素依赖性女性癌症治疗前后的血清铁蛋白和钙水平,并解读了它们在肿瘤复发和转移中的作用。

材料与方法

本回顾性研究已获得GIMSR机构伦理委员会(编号:GIMSR/Admn./Ethics/approval/IEC - 3/2021)和欧米伽癌症医院(注册号:ECR/1486/Inst/AP/2020)的批准。使用自动生物分析仪和夹心酶联免疫吸附测定(ELISA)对197份诊断为乳腺癌、宫颈癌和卵巢癌的临床样本(99份治疗前和98份治疗后)以及10份血液样本的铁蛋白和钙进行了分析。

结果

激素依赖性女性癌症治疗前后患者的铁蛋白水平均升高,而钙水平呈逐渐下降趋势。治疗前铁蛋白的平均值为0.0409mg/dL,而治疗后激素依赖性女性癌症患者的铁蛋白平均值为0.0428mg/dL。

结论

我们的结果表明,癌症治疗后患者的低钙血症会导致铁蛋白积累,这可能使这些患者更容易发生肿瘤复发和转移。

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本文引用的文献

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Hypocalcemia in cancer patients: An exploratory study.癌症患者的低钙血症:一项探索性研究。
Porto Biomed J. 2019 Jul 8;4(4):e45. doi: 10.1097/j.pbj.0000000000000045. eCollection 2019 Jul-Aug.
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Regulation of Gene Expression under Hypoxic Conditions.缺氧条件下的基因表达调控。
Int J Mol Sci. 2019 Jul 3;20(13):3278. doi: 10.3390/ijms20133278.
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Dysregulation of iron metabolism in cancer stem cells.癌细胞中铁代谢的失调。
Free Radic Biol Med. 2019 Mar;133:216-220. doi: 10.1016/j.freeradbiomed.2018.07.015. Epub 2018 Jul 21.
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Hypokalemia: a clinical update.低钾血症:临床最新进展
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