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基于血液游离 microRNAs 的非侵入性多癌种检测。

Noninvasive multi-cancer detection using blood-based cell-free microRNAs.

机构信息

Del Norte High School, San Diego, CA, USA.

Department of Pharmacology, Physiology & Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

出版信息

Sci Rep. 2024 Sep 27;14(1):22136. doi: 10.1038/s41598-024-73783-0.

DOI:10.1038/s41598-024-73783-0
PMID:39333750
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11436735/
Abstract

Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age- and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of 4,875 cancer patients across 13 cancer types and 3,722 non-cancer participants, the 4-microRNA model achieved greater than 90% sensitivity for 9 cancer types (lung, biliary tract, bladder, colorectal, esophageal, gastric, glioma, pancreatic, and prostate cancers) and 75-84% sensitivity for 3 cancer types (sarcoma, liver, and ovarian cancer), while maintaining greater than 99% specificity. The sensitivity remained to be > 99% for patients with stage 1 lung cancer. Our study provided novel evidence to support the development of an inexpensive and accurate miRNA-based blood test for multi-cancer early detection.

摘要

与晚期疾病患者相比,早期癌症患者的生存机会要高得多。然而,早期癌症筛查的选择有限,大多数癌症类型缺乏有效的筛查工具。在这里,我们报告了一种基于癌症患者和对照的血清 microRNA 微阵列数据检测的多癌种早期检测的 miRNA 为基础的血液检测。首先,使用来自 7 种癌症类型的 1408 名患者和 1408 名年龄和性别匹配的非癌症对照者的大型多癌种训练集,使用 10 倍交叉验证开发了一个 4 个 microRNA 的诊断模型。在三个独立的验证集中,总共有 13 种癌症类型的 4875 名癌症患者和 3722 名非癌症参与者,4 个 microRNA 模型对 9 种癌症(肺癌、胆管癌、膀胱癌、结直肠癌、食管癌、胃癌、神经胶质瘤、胰腺癌和前列腺癌)的敏感性大于 90%,对 3 种癌症(肉瘤、肝癌和卵巢癌)的敏感性为 75-84%,同时保持大于 99%的特异性。对于 1 期肺癌患者,其敏感性仍大于 99%。我们的研究为开发一种廉价且准确的基于 miRNA 的多癌种早期检测血液检测提供了新的证据支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/7f0d9d81c64b/41598_2024_73783_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/89a382f0405d/41598_2024_73783_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/922d1d42f16a/41598_2024_73783_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/220a4cf9094c/41598_2024_73783_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/c86fe712340c/41598_2024_73783_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/7f0d9d81c64b/41598_2024_73783_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/89a382f0405d/41598_2024_73783_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/922d1d42f16a/41598_2024_73783_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/220a4cf9094c/41598_2024_73783_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/c86fe712340c/41598_2024_73783_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbda/11436735/7f0d9d81c64b/41598_2024_73783_Fig5_HTML.jpg

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