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整合素α6转录本在粪便mRNA检测中用于检测可治愈阶段结直肠癌的应用。

Use of integrin alpha 6 transcripts in a stool mRNA assay for the detection of colorectal cancers at curable stages.

作者信息

Beaulieu Jean-François, Herring Elizabeth, Kanaoka Shigeru, Tremblay Éric

机构信息

Laboratory of Intestinal Physiopathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.

Department of Gastroenterology, Hamamatsu Medical Center, Hamamatsu, Japan.

出版信息

Oncotarget. 2016 Mar 22;7(12):14684-92. doi: 10.18632/oncotarget.7407.

Abstract

OBJECTIVE

An important criterion for colorectal cancer (CRC) screening is the ability to detect lesions at a curable stage. In the present study, we have assessed the integrin α6 subunit transcript (ITGA6) as part of a stool assay for the detection of colorectal lesions.

RESULTS

In comparison with control samples, ITGA6 levels were found to be significantly increased at all stages (P < 0.01). Receiver operating characteristic analysis revealed areas under the curve of 0.89 for the prediction of CRC with 81% sensitivity and 88% specificity and of 0.90 for the prediction of advanced adenomas (Ad) with 75% sensitivity and 88% specificity. The ITGA6A variant was also found to be increased relative to ITGA6 in stage II and III CRCs. Combining ITGA6 with other selected transcripts and/or immunochemical fecal occult blood test (iFOBT) results further increased sensitivity and specificity for the detection of colorectal lesions.

PATIENTS AND METHODS

ITGA6 detection used alone and under various combinations including detection of other mRNA markers and iFOBT was assessed on stool samples obtained from 175 patients (91 CRCs, 24 Ad and 60 healthy controls).

CONCLUSIONS

These data confirm the usefulness and reliability of an mRNA stool assay for the detection of colorectal lesions. The validation of additional candidate genes and their analysis in multiplex qPCR represents a powerful and robust approach that can be combined with iFOBT results to improve the detection of colorectal lesions.

摘要

目的

结直肠癌(CRC)筛查的一项重要标准是能够在可治愈阶段检测出病变。在本研究中,我们评估了整合素α6亚基转录本(ITGA6)作为粪便检测的一部分用于检测结直肠病变。

结果

与对照样本相比,发现ITGA6水平在所有阶段均显著升高(P < 0.01)。受试者工作特征分析显示,预测CRC时曲线下面积为0.89,灵敏度为81%,特异性为88%;预测进展期腺瘤(Ad)时曲线下面积为0.90,灵敏度为75%,特异性为88%。还发现ITGA6A变体相对于ITGA6在II期和III期CRC中有所增加。将ITGA6与其他选定的转录本和/或免疫化学粪便潜血试验(iFOBT)结果相结合,进一步提高了检测结直肠病变的灵敏度和特异性。

患者和方法

对从175例患者(91例CRC、24例Ad和60例健康对照)获得的粪便样本进行单独及包括检测其他mRNA标志物和iFOBT在内的各种组合情况下的ITGA6检测评估。

结论

这些数据证实了mRNA粪便检测用于检测结直肠病变的有效性和可靠性。对其他候选基因的验证及其在多重定量PCR中的分析是一种强大而稳健的方法,可与iFOBT结果相结合以改善结直肠病变的检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c65/4924744/3fcaf54c0fac/oncotarget-07-14684-g001.jpg

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