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寻求泛癌诊断/预后的研究最终以检测外周血中 Oct4A 的 HrC 测试为终点。

Quest for Pan-Cancer Diagnosis/Prognosis Ends with HrC Test Measuring Oct4A in Peripheral Blood.

机构信息

Epigeneres Biotech Pvt Ltd., C-701, Ganpatrao Kadam Marg, Lower Parel, Mumbai, 400013, India.

ICMR - National Institute for Research in Reproductive Health, J Merwanji Street, Parel East, Parel, Mumbai, Maharashtra, 400012, India.

出版信息

Stem Cell Rev Rep. 2021 Oct;17(5):1827-1839. doi: 10.1007/s12015-021-10167-1. Epub 2021 May 6.

Abstract

Cancer is a devastating disease whose incidence has increased in recent times and early detection can lead to effective treatment. Existing detection tools suffer from low sensitivity and specificity, and are high cost, invasive and painful procedures. Cancers affecting different tissues, ubiquitously express embryonic markers including Oct-4A, whose expression levels have also been correlated to staging different types of cancer. Cancer stem cells (CSCs) that initiate cancer are possibly the 'transformed' and pluripotent very small embryonic-like stem cells (VSELs) that also express OCT-4A. Excessive self-renewal of otherwise quiescent, pluripotent VSELs in normal tissues possibly initiates cancer. In an initial study on 120 known cancer patients, it was observed that Oct-4A expression in peripheral blood correlated well with the stage of cancer. Based on these results, we developed a proprietary HrC scale wherein fold change of OCT-4A was linked to patient status - it is a numerical scoring system ranging from non-cancer (0-2), inflammation (>2-6), high-risk (>6-10), stage I (>10-20), stage II (>20-30), stage III (>30-40), and stage IV (>40) cancers. Later the scale was validated on 1000 subjects including 500 non-cancer and 500 cancer patients. Ten case studies are described and show (i) HrC scale can detect cancer, predict and monitor treatment outcome (ii) is superior to evaluating circulating tumor cells and (iii) can also serve as an early biomarker. HrC method is a novel breakthrough, non-invasive, blood-based diagnostic tool that can detect as well as classify solid tumors, hematological malignancies and sarcomas, based on their stage.

摘要

癌症是一种毁灭性疾病,其发病率在最近有所增加,早期检测可以导致有效的治疗。现有的检测工具存在灵敏度和特异性低的问题,而且成本高、侵入性强、痛苦。影响不同组织的癌症普遍表达胚胎标志物,包括 Oct-4A,其表达水平也与不同类型癌症的分期相关。启动癌症的癌症干细胞(CSCs)可能是“转化的”和多能的非常小的胚胎样干细胞(VSELs),它们也表达 OCT-4A。正常组织中原本静止的、多能的 VSELs 的过度自我更新可能会引发癌症。在对 120 名已知癌症患者的初步研究中,观察到外周血中的 Oct-4A 表达与癌症分期密切相关。基于这些结果,我们开发了一种专有 HR 量表,其中 OCT-4A 的倍数变化与患者状态相关——这是一种数值评分系统,范围从非癌症(0-2)、炎症(>2-6)、高风险(>6-10)、I 期(>10-20)、II 期(>20-30)、III 期(>30-40)和 IV 期(>40)癌症。后来,该量表在包括 500 名非癌症患者和 500 名癌症患者在内的 1000 名受试者中进行了验证。描述了十个案例研究,表明(i)HR 量表可以检测癌症,预测和监测治疗效果(ii)优于评估循环肿瘤细胞,(iii)也可以作为早期生物标志物。HR 方法是一种新颖的突破,是一种非侵入性的血液诊断工具,可根据肿瘤的分期来检测和分类实体瘤、血液恶性肿瘤和肉瘤。

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