Signaling pathways activation profiles make better markers of cancer than expression of individual genes

Abstract

Identification of reliable and accurate molecular markers remains one of the major challenges of contemporary biomedicine. We developed a new bioinformatic technique termed OncoFinder that for the first time enables to quantatively measure activation of intracellular signaling pathways basing on transcriptomic data. Signaling pathways regulate all major cellular events in health and disease. Here, we showed that the Pathway Activation Strength (PAS) value itself may serve as the biomarker for cancer, and compared it with the “traditional” molecular markers based on the expression of individual genes. We applied OncoFinder to profile gene expression datasets for the nine human cancer types including bladder cancer, basal cell carcinoma, glioblastoma, hepatocellular carcinoma, lung adenocarcinoma, oral tongue squamous cell carcinoma, primary melanoma, prostate cancer and renal cancer, totally 292 cancer and 128 normal tissue samples taken from the Gene expression omnibus (GEO) repository. We profiled activation of 82 signaling pathways that involve ~2700 gene products. For 9/9 of the cancer types tested, the PAS values showed better area-under-the-curve (AUC) scores compared to the individual genes enclosing each of the pathways. These results evidence that the PAS values can be used as a new type of cancer biomarkers, superior to the traditional gene expression biomarkers.

Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Glioblastoma

“…Both individual gene expression and molecular pathway activation levels can be used for tumor diagnosis and prognosis of treatment outcomes [26][27][28][29]. However, the activation level of molecular pathways provides more robust biomarker signatures compared to individual genes [30,31]. Based on pathway activation analysis and expressions of drug target genes, an approach was proposed that makes it possible to personalize the ranking of anticancer target drugs (ATDs) for an individual tumor [27,32,33].…”

Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients

“…9 miRNAs have been shown to regulate many physiologic, developmental, and disease-associated processes, including cancer development 10 and inflammatory 11 and immune 12 piRNAs comprise another class of sncRNAs with lengths of 26 to 32 nt that bind PIWI proteins. Originally, piRNAs were thought to be involved in germ cell genome protection through epigenetic and posttranscriptional silencing of transposable elements, 13 but recent findings demonstrate their presence and activity also in somatic cells, [14][15][16][17] in which their function is still not fully understood.…”

Oxidative Status Pathways: Systemic Biomarkers

“…Other labs also successfully apply pathway activation-based technologies in various field and other sample types, with special attention paid to fresh solid tumors samples and paraffin blocks [68]. Of note, Oncofinder technology [69,70] and Oncotype DX assay [71] are among the most effective interactomics/multi-gene analysis-based tests in oncology.…”