Association between Expression of Connective Tissue Genes and Prostate Cancer Growth and Progression.
Patrick-Julien TreacyAlberto MartiniUgo Giovanni FalagarioParita RatnaniEthan WajswolAlp Tuna BeksacPeter WiklundSujit S NairNatasha KyprianouMatthieu DurandAshutosh K TewariPublished in: International journal of molecular sciences (2023)
To find an association between genomic features of connective tissue and pejorative clinical outcomes on radical prostatectomy specimens. We performed a retrospective analysis of patients who underwent radical prostatectomy and underwent a Decipher transcriptomic test for localized prostate cancer in our institution ( n = 695). The expression results of selected connective tissue genes were analyzed after multiple t tests, revealing significant differences in the transcriptomic expression (over- or under-expression). We investigated the association between transcript results and clinical features such as extra-capsular extension (ECE), clinically significant cancer, lymph node (LN) invasion and early biochemical recurrence (eBCR), defined as earlier than 3 years after surgery). The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic role of genes on progression-free survival (PFS) and overall survival (OS). Out of 528 patients, we found that 189 had ECE and 27 had LN invasion. The Decipher score was higher in patients with ECE, LN invasion, and eBCR. Our gene selection microarray analysis showed an overexpression in both ECE and LN invasion, and in clinically significant cancer for COL1A1 , COL1A2 , COL3A1 , LUM , VCAN , FN1 , AEBP1 , ASPN , TIMP1 , TIMP3 , BGN , and underexpression in FMOD and FLNA . In the TCGA population, overexpression of these genes was correlated with worse PFS. Significant co-occurrence of these genes was observed. When presenting overexpression of our gene selection, the 5-year PFS rate was 53% vs. 68% ( p = 0.0315). Transcriptomic overexpression of connective tissue genes correlated to worse clinical features, such as ECE, clinically significant cancer and BCR, identifying the potential prognostic value of the gene signature of the connective tissue in prostate cancer. TCGAp cohort analysis showed a worse PFS in case of overexpression of the connective tissue genes.
Keyphrases
- single cell
- prostate cancer
- radical prostatectomy
- rna seq
- genome wide
- genome wide identification
- papillary thyroid
- transcription factor
- poor prognosis
- bioinformatics analysis
- genome wide analysis
- free survival
- copy number
- cell proliferation
- lymph node
- dna methylation
- acute lymphoblastic leukemia
- cell migration
- squamous cell
- chronic kidney disease
- end stage renal disease
- lymph node metastasis
- ejection fraction
- high resolution
- patient reported outcomes
- early stage
- peritoneal dialysis
- single molecule