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CLIC1 和 CLIC4 与 CA125 一起作为所有上皮性卵巢癌亚型的诊断生物标志物组合。

CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer.

机构信息

Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, 19104, USA.

Department of Obstetrics and Gynecology, University of Colorado, Aurora, Colorado, 80045, USA.

出版信息

Sci Rep. 2018 Oct 3;8(1):14725. doi: 10.1038/s41598-018-32885-2.

DOI:10.1038/s41598-018-32885-2
PMID:30282979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6170428/
Abstract

New plasma and tissue biomarkers of epithelial ovarian cancer (EOC) could improve early diagnosis and post-diagnosis clinical management. Here we investigated tissue staining and tissue secretion of CLIC1 and CLIC4 across EOC subtypes. CLIC1 and CLIC4 are two promising biomarkers we previously showed were elevated in EOC patient sera. Individually, CLIC1 or CLIC4 stained larger percentages of malignant tumors across all EOC subtypes compared with CA125, particularly early stage and mucinous tumors. CLIC4 also stained benign tumors but staining was limited to nuclei; whereas malignant tumors showed diffuse cellular staining of stromal and tumor cells. Both proteins were shed by all EOC subtypes tumors in short term organ culture at more consistent levels than CA125, supporting their potential as pan-subtype serum and tissue biomarkers. Elevated CLIC4 expression, but not CLIC1 expression, was a negative indicator of patient survival, and CLIC4 knockdown in cultured cells decreased cell proliferation and migration indicating a potential role in tumor progression. These results suggest CLIC1 and CLIC4 are promising serum and tissue biomarkers as well as potential therapeutic targets for all EOC subtypes. This justifies development of high throughput serum/plasma biomarker assays to evaluate utility of a biomarker panel consisting of CLIC1, CLIC4 and CA125.

摘要

新的上皮性卵巢癌 (EOC) 血浆和组织生物标志物可以改善早期诊断和诊断后的临床管理。在这里，我们研究了 CLIC1 和 CLIC4 在各种 EOC 亚型中的组织染色和组织分泌情况。CLIC1 和 CLIC4 是我们之前在 EOC 患者血清中发现升高的两种很有前途的生物标志物。单独来看，CLIC1 或 CLIC4 在所有 EOC 亚型中的恶性肿瘤染色百分比均高于 CA125，尤其是早期和黏液性肿瘤。CLIC4 也染色良性肿瘤，但仅限于细胞核；而恶性肿瘤则表现为基质和肿瘤细胞的弥漫性细胞染色。在短期器官培养中，所有 EOC 亚型肿瘤都分泌这两种蛋白质，其水平比 CA125 更为一致，支持它们作为泛亚型血清和组织生物标志物的潜力。CLIC4 表达升高而非 CLIC1 表达升高是患者生存的负向指标，培养细胞中的 CLIC4 敲低可降低细胞增殖和迁移，表明其在肿瘤进展中可能具有作用。这些结果表明 CLIC1 和 CLIC4 是有前途的血清和组织生物标志物，也是所有 EOC 亚型的潜在治疗靶点。这证明了开发高通量血清/血浆生物标志物检测方法的合理性，以评估由 CLIC1、CLIC4 和 CA125 组成的生物标志物组合的效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/cd6bfbb863aa/41598_2018_32885_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/72e3c73cc68e/41598_2018_32885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/1829bf15f321/41598_2018_32885_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/196e708d0453/41598_2018_32885_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/e188e480a826/41598_2018_32885_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/be07bfd6a5a9/41598_2018_32885_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/1f6027ff4957/41598_2018_32885_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/cd6bfbb863aa/41598_2018_32885_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/72e3c73cc68e/41598_2018_32885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/1829bf15f321/41598_2018_32885_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/196e708d0453/41598_2018_32885_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/e188e480a826/41598_2018_32885_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/be07bfd6a5a9/41598_2018_32885_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/1f6027ff4957/41598_2018_32885_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b870/6170428/cd6bfbb863aa/41598_2018_32885_Fig7_HTML.jpg

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