Expression of Androgen and Estrogen Signaling Components and Stem Cell Markers to Predict Cancer Progression and Cancer-Specific Survival in Patients with Metastatic Prostate Cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Specific Antigen ◽  
Estrogen Signaling ◽  
Stem Cell Markers ◽  
Clinical Failure ◽  
Cancer Specific Survival ◽  
Validation Set ◽  
Signaling Components

Purpose: Genes of androgen and estrogen signaling cells and stem cell–like cells play crucial roles inprostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes.Experimental Design: We developed models to predict clinical failure using biopsy samples from atraining set of 46 and an independent validation set of 30 patients with treatment-na€?ve prostate cancer withbone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection.We analyzed the association between clinical failure andmRNAexpression of the following genes androgenreceptor (AR) and its related genes (APP, FOX family, TRIM 36, Oct1, and ACSL 3), stem cell–like molecules(Klf4, c-Myc, Oct 3/4, and Sox2), estrogen receptor (ER), Her2, PSA, and CRP.Results: Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under thecurve (AUC) of 1.0 in both sets for Sox2, Her2, and CRP expression in cancer cells, AR and ERa expression instromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS):Oct1, TRIM36, Sox2, and c-Myc expression in cancer cells; AR, Klf4, and ERa expression in stromal cells; andPSA, Gleason score, and extent of disease.Onthe basis of these factors, patients were divided into favorable-,intermediate-, and poor-risk groups according to the number of factors present. Five-year CSS rates for the 3groups were 90%, 32%, and12%in the training set and 75%, 48%, and0%in the validation set, respectively.Conclusions: Expression levels of androgen- and estrogen signaling components and stem cell markersare powerful prognostic tools.

Preferential interaction of platelets with prostate cancer cells with stem cell markers

2021 ◽  
Author(s):  
Jan K. Rudzinski ◽  
Natasha P. Govindasamy ◽  
Amir Asgari ◽  
Max Saito ◽  
John D. Lewis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Stem Cell Markers ◽  
Prostate Cancer Cells ◽  
Cell Markers ◽  
Preferential Interaction

scholarly journals Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Ajai J. Pulianmackal ◽  
Dan Sun ◽  
Kenji Yumoto ◽  
Zhengda Li ◽  
Yu-Chih Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Stem Cell ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Recurrence ◽  
Stem Cell Markers ◽  
Prostate Cancer Cells ◽  
Altered Expression ◽  
Cancer Dormancy

The proliferation-quiescence decision is a dynamic process that remains incompletely understood. Live-cell imaging with fluorescent cell cycle sensors now allows us to visualize the dynamics of cell cycle transitions and has revealed that proliferation-quiescence decisions can be highly heterogeneous, even among clonal cell lines in culture. Under normal culture conditions, cells often spontaneously enter non-cycling G0 states of varying duration and depth. This also occurs in cancer cells and G0 entry in tumors may underlie tumor dormancy and issues with cancer recurrence. Here we show that a cell cycle indicator previously shown to indicate G0 upon serum starvation, mVenus-p27K-, can also be used to monitor spontaneous quiescence in untransformed and cancer cell lines. We find that the duration of spontaneous quiescence in untransformed and cancer cells is heterogeneous and that a portion of this heterogeneity results from asynchronous proliferation-quiescence decisions in pairs of daughters after mitosis, where one daughter cell enters or remains in temporary quiescence while the other does not. We find that cancer dormancy signals influence both entry into quiescence and asynchronous proliferation-quiescence decisions after mitosis. Finally, we show that spontaneously quiescent prostate cancer cells exhibit altered expression of components of the Hippo pathway and are enriched for the stem cell markers CD133 and CD44. This suggests a hypothesis that dormancy signals could promote cancer recurrence by increasing the proportion of quiescent tumor cells poised for cell cycle re-entry with stem cell characteristics in cancer.

scholarly journals O7: APPARENT PATHOLOGICAL COMPLETE RESPONSE TO NEOADJUVANT THERAPY LEADS TO SELECTION OF TREATMENT RESISTANT CANCER STEM CELLS IN OESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
RC Walker ◽  
J Harrington ◽  
B Grace ◽  
M Lloyd ◽  
JP Byrne ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Rna Sequencing ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Oesophageal Adenocarcinoma ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
Resistance To Therapy

Abstract Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

Sign in / Sign up

Export Citation Format

Share Document