Comprehensive analysis of normal adjacent to tumor transcriptomes

Abstract

Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies. However, little is known about the transcriptomic profile of NAT, how it is influenced by the tumor, and how the profile compares with non-tumor-bearing tissues. Here, we integrate data from the Genotype-Tissue Expression project and The Cancer Genome Atlas to comprehensively analyze the transcriptomes of healthy, NAT, and tumor tissues in 6506 samples across eight tissues and corresponding tumor types. Our analysis shows that NAT presents a unique intermediate state between healthy and tumor. Differential gene expression and protein–protein interaction analyses reveal altered pathways shared among NATs across tissue types. We characterize a set of 18 genes that are specifically activated in NATs. By applying pathway and tissue composition analyses, we suggest a pan-cancer mechanism of pro-inflammatory signals from the tumor stimulates an inflammatory response in the adjacent endothelium.

5‐Hydroxymethylcytosine as a clinical biomarker: Fluorescence‐based assay for high‐throughput epigenetic quantification in human tissues

“…We show that despite the high variability between individuals, in most cases, the adjacent tissue already displays molecular reduction of 5‐hmC level relative to the healthy baseline average. These results are in line with recent studies reporting that the gene expression profile of such tissues may indicate an intermediate state, between healthy and tumor . We note that the absolute 5‐hmC levels of tumor and adjacent tissue are highly patient dependent, suggesting a need for personalized diagnostics.…”

“…Such tissue regions, despite displaying normal morphology may in some cases present reduced 5‐hmC levels, providing a quantitative molecular indication for the state of the examined tissue. Such intermediate states were recently revealed by differential gene expression and protein–protein interaction analysis . We show similar changes in pancreatic tumors and matched adjacent tissue.…”

Integrative factorization of bidimensionally linked matrices

“…However, such analyses do not address the molecular heterogeneity or trans-omic interactions that characterize cancer cells. Noticeably, Aran et al (2017) conducted a comprehensive study on NAT across different cancers using TCGA and the Genotype-Tissue Expression (GTEx) program data and showed that the expression levels of NAT from breast, colon, liver, lung, and uterine tumors yield different clustering from their respective tumor tissues. In addition, Huang et al (2016), using TCGA data, suggested that NATs not only serve as controls to tumor tissues but also provide useful information on patients' survival, which tumor samples do not.…”

“…Noticeably, Aran et al . () conducted a comprehensive study on NAT across different cancers using TCGA and the Genotype‐Tissue Expression (GTEx) program data and showed that the expression levels of NAT from breast, colon, liver, lung, and uterine tumors yield different clustering from their respective tumor tissues. In addition, Huang et al .…”

The Emerging Role of Cytoskeletal Proteins as Reliable Biomarkers

“…This review highlights a number of cytoskeletal proteins, which are consistently regulated. Instead of random mutations leading to a regulation which favors migration, these regulations can be well orchestrated, for example by members of the miR‐200 family, which plays a significant role in epithelial phenotype tumors . The EMT gene signature has been identified in a number of tumors, as for example in the TCGA cohort.…”