TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues

Abstract

Genes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation and can serve as biomarkers of progression or as potential therapy targets. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web platform which enables the mining of this database by comparing normal, tumor and metastatic data across all genes in real time. We utilized data generated by either gene arrays from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or RNA-seq from The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories. The altered expression within different platforms was analyzed separately. Statistical significance was computed using Mann–Whitney or Kruskal–Wallis tests. False Discovery Rate (FDR) was computed using the Benjamini–Hochberg method. The entire database contains 56,938 samples, including 33,520 samples from 3180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3691 normal samples), 11,010 samples from TCGA (394 metastatic, 9886 tumorous and 730 normal), 1193 samples from TARGET (1 metastatic, 1180 tumorous and 12 normal) and 11,215 normal samples from GTEx. The most consistently upregulated genes across multiple tumor types were TOP2A (FC = 7.8), SPP1 (FC = 7.0) and CENPA (FC = 6.03), and the most consistently downregulated gene was ADH1B (FC = 0.15). Validation of differential expression using equally sized training and test sets confirmed the reliability of the database in breast, colon, and lung cancer at an FDR below 10%. The online analysis platform enables unrestricted mining of the database and is accessible at TNMplot.com.

Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

“…Finally, since our results show differences depending on the type of cell line (Luminal MCF-7 and triple-negative/basal MDA-MB-231), we analyzed the differential expression of Sdc-1 in non-tumor, primary tumors and metastases tissues from breast cancer patients. For this purpose, we use the online tool TNMplot (https://www.tnmplot.com, accessed on 21 May 2021) [35]. We observed that (1) Sdc-1 is more highly expressed in the primary and metastatic tumor tissues than in non-tumor samples and (2) Sdc-1 is expressed at higher levels in primary tissues than in metastatic sites (Supplementary Figure S3A).…”

“…The TNMplot database (https://www.tnmplot.com/, accessed on 21 May 2021) [35] was set up using the RNA-seq from The Cancer Genome Atlas (TCGA) repository. The database contains 11,010 samples from TCGA: 394 metastatic, 9886 tumorous and 730 normal tissues.…”

“…Normal, primary tumors and metastatic tissues gene comparison were also analyzed using Kruskal-Wallis test. The statistical significance cutoff was set at p < 0.01 [35]. For the survival analysis, the publicly available gene expression database Kaplan-Meier plotter (KM plotter) (https://kmplot.com/analysis/index.php?p=service& cancer=breast, accessed on 21 May 2021) was used [36].…”

“…Institutional Review Board Statement: All patient survival data were retrieved using the online tools kmplot.com and TNMPlot, which combine publically available GEO datasets. The datasets are described in references [35,36].…”

3-D Vascularized Breast Cancer Model to Study the Role of Osteoblast in Formation of a Pre-Metastatic Niche

“…Each of the highly upregulated genes was loaded into TNM plotter (BRCA database) to observe the differences in their expression in normal, cancerous and metastatic tissues (Figure S4a-e). 36 We observed that all the top five upregulated genes in NHMO samples as compared to NHM samples were expressed more in cancerous and metastatic breast cancer tissues as compared to normal breast tissues (Figure S4a-e). The gene signature consisting of all the five upregulated genes was observed to be expressed more in both TNBC and broad BRCA tissue database (fed into GEPIA2 application) as compared to normal tissue database (Figure S4f).…”