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A Novel Panel of 80 RNA Biomarkers with Differential Expression in Multiple Human Solid Tumors against Healthy Blood Samples.

ABSTRACT: The aim of this study was to identify genes with higher expression in solid tumor cells by comparing human tumor biopsies with healthy blood samples using both in silico statistical analysis and experimental validations. This approach resulted in a novel panel of 80 RNA biomarkers with high discrimination power to detect circulating tumor cells in blood samples. To identify the 80 RNA biomarkers, Affymetrix HG-U133 plus 2.0 microarrays datasets were used to compare breast tumor tissue biopsies and breast cancer cell lines with blood samples from patients with conditions other than cancer. A total of 859 samples were analyzed at the discovery stage, consisting of 417 mammary tumors, 41 breast lines, and 401 control samples. To confirm this discovery, external datasets of eight types of tumors were used, and experimental validation studies (NanoString n-counter gene expression assay) were performed, totaling 5028 samples analyzed. In these analyses, the 80 biomarkers showed higher expression in all solid tumors analyzed relative to healthy blood samples. Experimental validation studies using NanoString assay confirmed the results were not dependent of the gene expression platform. A panel of 80 RNA biomarkers was described here, with the potential to detect solid tumor cells present in the blood of multiple tumor types.

SUBMITTER: Delmonico L

PROVIDER: S-EPMC6802086 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A Novel Panel of 80 RNA Biomarkers with Differential Expression in Multiple Human Solid Tumors against Healthy Blood Samples.

Delmonico Lucas L Obenauer John C JC Qureshi Fatir F Alves Gilda G Costa Mauricio Augusto Silva Magalhães MASM Martin Katherine J KJ Fournier Marcia V MV

International journal of molecular sciences 20191002 19

The aim of this study was to identify genes with higher expression in solid tumor cells by comparing human tumor biopsies with healthy blood samples using both in silico statistical analysis and experimental validations. This approach resulted in a novel panel of 80 RNA biomarkers with high discrimination power to detect circulating tumor cells in blood samples. To identify the 80 RNA biomarkers, Affymetrix HG-U133 plus 2.0 microarrays datasets were used to compare breast tumor tissue biopsies a ...[more]

PMID: 31581693

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Project description:RNA samples from the blood of patients with double tumors, single tumors and from healthy control subjects are studied by gene expression analysis using the whole genome microarray platform AB1700 from Applied Biosystems. Gene expression profiles are derived from the microarray raw data by biostatistical analysis. Differential gene expression between the study subgroups and categories is assessed: On the one hand, all possible pairwise comparisons between the subgroups A, B, C, D, E and N are made in order to elucidate characteristics of the individual subgroups. On the other hand, the higher-ranked categories “double cancer” (AB, consisting of subgroups A and B) and “single cancer” (category CDE, consisting of subgroups C, D and E) are compared to each other and to the normal controls (N). Finally, the category “double cancer” is compared to the different single cancer subgroups (C, D and E). Analysis on the level of the higher ranked categories “double cancer” and “single cancer” aims at identifying the common traits of patients who have developed two independent tumors, as opposed to patients with only one tumor entity and to healthy individuals. Based on the functional annotation of the induced and repressed genes found in these comparisons, biological processes and pathways which are differentially activated in the subgroups or categories are identified, thus providing insights into their molecular characteristics. Furthermore, gene expression data are used to derive classifier rules, which are aimed at discriminating subjects from the different subgroups and categories and may constitute the basis for a future diagnostic classification tool. Keywords: microarray analysis, double-single primary malignancies A total of 66 individuals were analyzed:The primary study group consisted of 24 patients with two primary malignancies (group AB) (one of the primaries being of the breast, colon or ovary). The four control groups consisted of a total of 33 single cancer patiens: 10 with colon cancer (group C), 14 with breast cancer (group D), 9 with ovarian cancer (group E_) and 10 healthy individuals (group N). 4 samples (GECM-061_14, GECM-061_37, GECM-061_54 and GECM-061_72) were identifed as outliers by MA plots and therfore they were excluded from the study.

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A Novel Panel of 80 RNA Biomarkers with Differential Expression in Multiple Human Solid Tumors against Healthy Blood Samples.

Publications

A Novel Panel of 80 RNA Biomarkers with Differential Expression in Multiple Human Solid Tumors against Healthy Blood Samples.

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