Endosomal gene expression: a new indicator for prostate cancer patient prognosis?

Abstract

Prostate cancer continues to be a major cause of morbidity and mortality in men, but a method for accurate prognosis in these patients is yet to be developed. The recent discovery of altered endosomal biogenesis in prostate cancer has identified a fundamental change in the cell biology of this cancer, which holds great promise for the identification of novel biomarkers that can predict disease outcomes. Here we have identified significantly altered expression of endosomal genes in prostate cancer compared to non-malignant tissue in mRNA microarrays and confirmed these findings by qRT-PCR on fresh-frozen tissue. Importantly, we identified endosomal gene expression patterns that were predictive of patient outcomes. Two endosomal tri-gene signatures were identified from a previously published microarray cohort and had a significant capacity to stratify patient outcomes. The expression of APPL1, RAB5A, EEA1, PDCD6IP, NOX4 and SORT1 were altered in malignant patient tissue, when compared to indolent and normal prostate tissue. These findings support the initiation of a case-control study using larger cohorts of prostate tissue, with documented patient outcomes, to determine if different combinations of these new biomarkers can accurately predict disease status and clinical progression in prostate cancer patients.

Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass

“…50,51 Few of the tested markers showed decreasing transcript levels including ALIX, which was one of the most widely examined exosome markers in cancer development. 29,30,52,53 Our gene expression data correlated well with those gained from independent databases, [36][37][38][39] showing similarly reduced ALIX mRNA levels during adenoma-carcinoma sequence, which was also validated at the in situ protein level. Similar alterations between whole biopsy mRNA and protein level in epithelial compartment suggest that the majority of ALIX originated from these components.…”

“…3,[25][26][27] ALIX has been tested widely in exosome studies of colorectal carcinoma cell cultures 9,28 and has shown diagnostic and prognostic significance in different tumors. [29][30][31] Besides testing the transcript levels, here we determined ALIX protein expression in situ in the epithelial and stromal compartment including α-smooth muscle actin (SMA)-positive cells in low-and high-grade dysplastic adenomas as well as non-metastatic and metastatic (both lymph node and distant) colorectal carcinomas with particular focus on individual Musashi1-positive cancer stem cells at the tumor front.…”

APPL1-Mediating Leptin Signaling Contributes to Proliferation and Migration of Cancer Cells

“…Currently, APPL1 protein was found to be highly expressed in some tumor tissues such as aggressive prostate cancer tissues [15, 16]. Silencing of APPL1 resulted in a decrease in TGFβ-induced invasion of both human prostate cancer PC-3U cells and breast carcinoma MDA-MB-231 cells [15].…”

Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis

“…Changes in the expression of endosomal markers can have prognostic value in prostate cancers (Johnson et al, 2015). Here, we have shown that adaptive CME in NSCLC cells, resulting from upregulation of CLCb, increases cell migration and metastasis through a Dyn1-dependent mechanism.…”

“…Grb2 interacts with dynamin’s proline/arginine-rich domain (Solomaha et al, 2005). Interestingly, recent data have suggested that a tri-gene signature of high levels of expression of the early endosomal markers APPL1, EEA1, and rab5 strongly correlates with reduced survival in prostate cancer patients (Johnson et al, 2015). …”