Trends in Gene Expression Profiling for Prostate Cancer Risk Assessment: A Systematic Review

Objectives: The aim of the study is to review biotechnology advances in gene expression profiling on prostate cancer (PCa), focusing on experimental platform development and gene discovery, in relation to different study designs and outcomes in order to understand how they can be exploited to improve PCa diagnosis and clinical management. Methods: We conducted a systematic literature review on gene expression profiling studies through PubMed/MEDLINE and Web of Science between 2000 and 2016. Tissue biopsy and clinical gene profiling studies with different outcomes (e.g., recurrence, survival) were included. Results: Over 3,000 papers were screened and 137 full-text articles were selected. In terms of technology used, microarray is still the most popular technique, increasing from 50 to 70% between 2010 and 2015, but there has been a rise in the number of studies using RNA sequencing (13% in 2015). Sample sizes have increased, as well as the number of genes that can be screened all at once, but we have also observed more focused targeting in more recent studies. Qualitative analysis on the specific genes found associated with PCa risk or clinical outcomes revealed a large variety of gene candidates, with a few consistent cross-studies. Conclusions: The last 15 years of research in gene expression in PCa have brought a large volume of data and information that has been decoded only in part, but advancements in high-throughput sequencing technology are increasing the amount of data that can be generated. The variety of findings warrants the execution of both validation studies and meta-analyses. Genetic biomarkers have tremendous potential for early diagnosis of PCa and, if coupled with other diagnostics (e.g., imaging), can effectively be used to concretize less-invasive, personalized prediction of PCa risk and progression.

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Discovery of prostate cancer biomarkers by microarray gene expression profiling

Expert Review of Molecular Diagnostics ◽

10.1586/erm.09.74 ◽

2010 ◽

Vol 10 (1) ◽

pp. 49-64 ◽

Cited By ~ 49

Author(s):

Karina Dalsgaard Sørensen ◽

Torben Falck Ørntoft

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Cancer Biomarkers ◽

Microarray Gene Expression ◽

Microarray Gene

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Novel method for rapid enrichment of high purity circulating tumor cells (CTCs) for prostate cancer (PCa) gene expression profiling.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.271 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 271-271

Author(s):

Gareth Morrison ◽

Nita Jojo ◽

Alexander Cunha ◽

Yucheng Xu ◽

Peggy S. Robinson ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Gene Expression Profiling ◽

High Purity ◽

Whole Blood ◽

Expression Profiling ◽

Cell Recovery ◽

Enrichment Method ◽

Qrt Pcr ◽

Cd45 Depletion

271 Background: CTC RNA analysis currently involves single cell recovery that is laborious and expensive, or alternatively lysis of preserved whole blood which yields RNA predominantly from leukocytes which vastly outnumber CTCs. To effectively characterize gene expression in large patient cohorts, new enrichment methodologies are needed that yield high purity CTC populations while preserving RNA integrity. Here we describe a simple yet robust method for enrichment of prostate CTCs for gene expression analysis. Methods: Blood was drawn with informed consent under an IRB-approved protocol. For initial optimization, CFSE-stained PCa cells were spiked into healthy blood and recovered using various combinations of 2 methods: microfluidic enrichment (Parsortix™ system) and CD45 depletion. For assay qualification, a prostate-specific multiplexed qRT-PCR gene expression panel was developed. Enrichment and gene expression were tested initially using PCa cell lines spiked into healthy blood, then metastatic castrate resistant prostate cancer (mCRPC) blood samples in parallel with CellSearch enumeration. Results: Optimal enrichment of live cells was achieved with CD45 depletion followed by microfluidic enrichment, resulting in an average spiked cell recovery of 30% and approximately 100 contaminating background leukocytes. Using this enrichment method, prostate specific genes were detectable by multiplexed qRT-PCR down to 25 cells spiked into 7.5 ml whole blood, and transcripts were not measurable in matched healthy blood controls. When applied to mCRPC patient blood containing CTCs by CellSearch, multiplexed qRT-PCR successfully detected prostate specific genes in all samples. Conclusions: We developed a novel enrichment method capable of rapidly and efficiently recovering live CTCs with high purity, free of magnetic beads and with very few background leukocytes. Captured cells yielded high-quality RNA with high sensitivity and specificity for prostate-specific transcripts. This approach is applicable to high throughput gene expression profiling assays and offers an alternative to laborious single cell recovery or non-cancer-specific whole blood fixation.

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Association of immune gene expression profiling with vinflunine clinical benefit in metastatic urothelial cancer (mUC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16034 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16034-e16034

Author(s):

Guillermo de Velasco ◽

Marta Dueñas ◽

Alejandra Bernardini ◽

Alvaro Pinto ◽

Teresa Alonso-Gordoa ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Clinical Benefit ◽

Expression Profiling ◽

Checkpoint Inhibitors ◽

Gene Profiling ◽

Immune Gene ◽

Similar Frequency ◽

Metastatic Urothelial Cancer ◽

Platinum Based Chemotherapy

e16034 Background: There are limited treatment options for mUC after platinum-based chemotherapy failure. Immune checkpoint inhibitors (ICI) have shown a durable benefit but only in a minority of patients (20-25%). Vinflunine remains as a therapeutic option without validated biomarkers. In this study, we sought to analyze the molecular determinants of vinflunine response in mUC. Methods: mUC patients from 4 University Hospitals in Spain who received second-line vinflunine after platinum-based chemotherapy were classified in non-responders (NR: progressive disease ≤3 months; N = 10) or responders (R: response ≥ 6 months, N = 14). Targeted- sequencing of 275 cancer-related genes and a PanCancer Immune Profiling Panel were performed on pre-treatment tumors. Selected genes were evaluated by RT-qPCR and protein expression was detected by immunohistochemistry. Results: The most common alteration, TP53 mutations, had a similar frequency in R (7/14, 50%) and NR (4/10, 40%). Mutations in 5 genes: ERBB3 (4/14; 28,6%), KTM2C (4/14; 28,6%), PI3KCA (4/14; 28,6%), ARID2 (3/14; 21,4%) and FGFR3 (3/14; 21,4%) were identified only in R. Mutations in ERBB4 (3/10, 33,3%) and BCOR (2/10, 20%) were identified only in NR. Estimated TMBs were not significantly different among the R (13 per Mb) and NR (9 per Mb) samples. According to gene expression profiling, NR had high cytotoxic cells infiltrate and T cells as well as high counts of TILs compared to R. In addition, expression of IDO, MAGE A4, and SOCS1, that has been associated with response to ICIs, were down-regulated in R compared with NR. Conclusions: Gene profiling showed that low-expression levels of immune-related genes are significantly associated with clinical benefit from vinflunine. Validation and complementary studies are ongoing in patients treated with ICIs.

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