Dataset Information

A qualitative transcriptional signature for the early diagnosis of colorectal cancer.

ABSTRACT: 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.

SUBMITTER: Guan Q

PROVIDER: S-EPMC6778657 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A qualitative transcriptional signature for the early diagnosis of colorectal cancer.

Guan Qingzhou Q Zeng Qiuhong Q Yan Haidan H Xie Jiajing J Cheng Jun J Ao Lu L He Jun J Zhao Wenyuan W Chen Kui K Guo You Y Guan Guoxian G Guo Zheng Z

Cancer science 20190903 10

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 tissu ...[more]

PMID: 31335996

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Project description:BACKGROUND:Currently, pathological examination of gastroscopy biopsy specimens is the gold standard for gastric cancer (GC) diagnosis. However, it has a false-negative rate of 10-20% due to inaccurate sampling locations and/or insufficient sampling amount. A signature should be developed to aid the early diagnosis of GC using biopsy specimens even when they are sampled from inaccurate locations. METHODS:We extracted a robust qualitative transcriptional signature, based on the within-sample relative expression orderings (REOs) of gene pairs, to discriminate both GC tissues and adjacent-normal tissues from non-GC gastritis, intestinal metaplasia and normal gastric tissues. RESULTS:A signature consisting of two gene pairs for GC diagnosis was identified and validated in data of both biopsy specimens and surgical resection specimens pooled from publicly available datasets measured by different laboratories with different platforms. For gastroscopy biopsy specimens, 96.20% of 79 non-GC tissues were correctly identified as non-GC, and 96.84% of 158 GC tissues and six of seven adjacent-normal tissues were correctly identified as GC. For surgical resection specimens, 98.37% of 2560 GC tissues and 97.28% of 221 adjacent-normal tissues were correctly identified as GC. Especially, 97.67% of the 257 GC patients at stage I were exactly diagnosed as GC. We additionally measured 21 GC tissues from seven different GC patients, each with three specimens sampled from three tumor locations with different proportions of the tumor epithelial cell. All these GC tissues were correctly identified as GC, even when the proportion of the tumor epithelial cell was as low as 14%. CONCLUSIONS:The qualitative transcriptional signature can distinguish both GC and adjacent-normal tissues from normal, gastritis and intestinal metaplasia tissues of non-GC patients even using inaccurately sampled biopsy specimens, which can be applied robustly at the individual level to aid the early GC diagnosis.

Project description:Background & aimsCurrently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate.MethodsBased on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients.ResultsA signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics.ConclusionsThe signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early diagnosis of hepatocellular carcinoma.

Dataset Information

A qualitative transcriptional signature for the early diagnosis of colorectal cancer.

Publications

A qualitative transcriptional signature for the early diagnosis of colorectal cancer.

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