Department of Bioinformatics, School of Basic Medical Sciences, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
Key Laboratory of Medical Bioinformatics, Fuzhou, China.
Cancer Sci. 2019 Oct;110(10):3225-3234. doi: 10.1111/cas.14137. Epub 2019 Sep 3.
Currently, using biopsy specimens for the early diagnosis of colorectal cancer (CRC) is not entirely reliable due to insufficient sampling amount and inaccurate sampling location. Thus, it is necessary to develop a signature that can accurately identify patients with CRC under these clinical scenarios. Based on the relative expression orderings of genes within individual samples, we developed a qualitative transcriptional signature to discriminate CRC tissues, including CRC adjacent normal tissues from non-CRC individuals. The signature was validated using multiple microarray and RNA sequencing data from different sources. In the training data, a signature consisting of 7 gene pairs was identified. It was well validated in both biopsy and surgical resection specimens from multiple datasets measured by different platforms. For biopsy specimens, 97.6% of 42 CRC tissues and 94.5% of 163 non-CRC (normal or inflammatory bowel disease) tissues were correctly classified. For surgically resected specimens, 99.5% of 854 CRC tissues and 96.3% of 81 CRC adjacent normal tissues were correctly identified as CRC. Notably, we additionally measured 33 CRC biopsy specimens by the Affymetrix platform and 13 CRC surgical resection specimens, with different proportions of tumor epithelial cells, ranging from 40% to 100%, by the RNA sequencing platform, and all these samples were correctly identified as CRC. The signature can be used for the early diagnosis of CRC, which is also suitable for minimum biopsy specimens and inaccurately sampled specimens, and thus has potential value for clinical application.
目前，由于活检样本的采样量不足和采样位置不准确，利用活检标本进行结直肠癌（CRC）的早期诊断并不完全可靠。因此，有必要开发一种能够在这些临床情况下准确识别 CRC 患者的标志物。我们基于单个样本中基因的相对表达顺序，开发了一种定性转录标志物来区分 CRC 组织，包括 CRC 相邻正常组织与非 CRC 个体。该标志物通过来自不同来源的多个微阵列和 RNA 测序数据集进行了验证。在训练数据中，确定了一个由 7 个基因对组成的标志物。该标志物在来自不同平台的多个数据集的活检和手术切除标本中得到了很好的验证。对于活检标本，42 个 CRC 组织中有 97.6%和 163 个非 CRC（正常或炎症性肠病）组织中有 94.5%被正确分类。对于手术切除标本，854 个 CRC 组织中有 99.5%和 81 个 CRC 相邻正常组织中有 96.3%被正确识别为 CRC。值得注意的是，我们还通过 RNA 测序平台额外测量了 33 个 CRC 活检标本和 13 个 CRC 手术切除标本，这些标本的肿瘤上皮细胞比例不同，范围从 40%到 100%，所有这些标本都被正确识别为 CRC。该标志物可用于 CRC 的早期诊断，也适用于最小活检标本和采样不准确的标本，因此具有潜在的临床应用价值。
