scholarly journals Exploring the extracellular transcriptome in seminal plasma for non-invasive prostate cancer diagnosis

Author(s):  
Eva Hulstaert ◽  
Annelien Morlion ◽  
Justine Nuytens ◽  
Giovanni Ponti ◽  
Monia Maccaferri ◽  
...  

A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gulfem D. Guler ◽  
Yuhong Ning ◽  
Chin-Jen Ku ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.


2021 ◽  
pp. 33-33
Author(s):  
Nasim Ebrahimi ◽  
Farzane Amirmahani ◽  
Maryam Akbari ◽  
Azin Ghahfarokhi ◽  
Bahareh Hajihashemi ◽  
...  

Several long non-coding RNAs (lncRNAs) have recently emerged as potential biomarkers in cancer biology. In the present study, we examined the expression of four lncRNAs (CAT179, CAT1796, PRCAT47, and CAT1066) to evaluate their ability to discriminate prostate tumors from benign prostate hyperplasia (BPH). Expression of these four lncRNAs was examined in 20 prostate cancer and 20 benign prostate hyperplasia (BPH) samples, as well as in urine samples (11 BPH, and 11 cancer). Total RNA was extracted for cDNA syntheses. The expression of the candidate lncRNAs was evaluated by quantitative real-time PCR (qRT-PCR). The lncRNAs CAT1796 and CAT179 were both upregulated in prostate cancer compared to BPH clinical samples (P<0.05). ROC curve analysis showed that CAT1796 had high sensitivity and specificity for diagnosis of prostate cancer (AUC=0.8151[95%CI 0.65-0.97]), suggesting that CAT1796 lncRNA could be a prostate cancer biomarker.


2011 ◽  
Vol 10 (2) ◽  
pp. 206-207
Author(s):  
J. Neuhaus ◽  
P. Von Wilcke ◽  
H.W. Bauer ◽  
E. Schiffer ◽  
J. Siwy ◽  
...  

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Andrej Jedinak ◽  
Adam Curatolo ◽  
David Zurakowski ◽  
Simon Dillon ◽  
Manoj K Bhasin ◽  
...  

Medicina ◽  
2011 ◽  
Vol 47 (3) ◽  
pp. 20
Author(s):  
Kristina Daniūnaitė ◽  
Artūras Berezniakovas ◽  
Feliksas Jankevičius ◽  
Arvydas Laurinavičius ◽  
Juozas Lazutka ◽  
...  

Background. Prostate cancer (PCa) is the second most prevalent malignancy among males, characterized by high mortality rates. Aberrant DNA methylation in promoters of tumor suppressor genes is an early and frequent event during prostate carcinogenesis. Modern techniques allow a sensitive detection of DNA methylation biomarkers in bodily fluids from cancer patients offering a noninvasive tool for PCa monitoring. Our study aimed at the analysis of DNA methylation in urine sediments from PCa patients for the selection of most informative noninvasive biomarkers. Material and Methods. Real-time methylation-specific polymerase chain reaction was used for the detection of methylated RASSF1, RARB, and GSTP1 genes in catheterized urine specimens from 34 patients with biopsy-proven early or medium stage PCa. Results. At least one gene was methylated in urine sediments from 28 cases with PCa, with a sensitivity of the test reaching 82%. RASSF1 was methylated in 71% (24 of 34), RARB in 44% (15 of 34), and GSTP1 in 3% (1 of 34) of the specimens. High level of methylation (≥50%) in RARB and RASSF1 genes was detected in 40% and 20% of cases, respectively. A significant association was observed between high level of RARB methylation and Gleason score (P=0.01), while methylation of at least one gene occurred more frequently in urine DNA of older patients (P=0.02). Conclusions. Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa.


2011 ◽  
Author(s):  
Adam S. Curatolo ◽  
Roopali Roy ◽  
Andrej Jedinak ◽  
Kevin Loughlin ◽  
Michael Meyers ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5162-5162
Author(s):  
H. R. Sanders ◽  
H. Li ◽  
K. Z. Qu ◽  
Z. J. Zhang ◽  
A. D. Sferruzza ◽  
...  

5162 Background: TMPRSS2 gene rearrangements have been reported in 40%-85% of prostate cancer (PCa) patients and have not been found in normal individuals or those with benign prostate hyperplasia (BPH). However, multiple partner genes, including ETS transcription genes, and breakpoints have been reported. We developed an assay based on TMPRSS2 5′ and 3′ intragenic differential expression (IDE) to potentially serve as a diagnostic or prognostic marker for PCa. Methods: We analyzed TMPRSS2 in FFPE tissue from 20 patients (9 PCa and 11 BPH) and plasma from 42 patients (32 PCa and 10 BPH). IDE was expressed as a ratio of 3′:5′ transcript levels which were determined by real-time RT-PCR using distinct primer/probe sets. A normal 3′:5′ ratio (≥30) was established by comparing nonmalignant cells to tumor cells from FFPE tissue. This cutoff was subsequently used to identify abnormal ratios in plasma specimens. Results: In FFPE tissue, 100% of PCa samples had a 3′:5′ratio <30 and 91% of BPH samples were ≥30 ( Table ). RNA in 48% of plasma samples passed our QC criteria for acceptability. The 3′:5′ ratios were <30 in 47% and ≥30 in 6.7% PCa plasma. Conclusions: By measuring IDE, we are not limited to screening for known TMPRSS2/ETS gene translocations. In tissue, this approach enabled us to identify patients with PCa vs. BPH with high specificity. Although work is needed to improve plasma RNA quality, IDE of plasma TMPRSS2 may be a useful non-invasive diagnostic or prognostic tool. [Table: see text] No significant financial relationships to disclose.


2021 ◽  
Vol 8 (2) ◽  
pp. 107-113
Author(s):  
Aydemir Asdemir ◽  
Sevgi Durna Dastan ◽  
Esat Korgali ◽  
Tugba Yildiz Asdemir ◽  
Huseyin Saygin ◽  
...  

Objective: It is necessary to provide PSA alternatives or methods that can be used in conjunction with PSA to regress complications rising from negative biopsies and to increase diagnostic value. Patients and Methods: The study is consisting of 59 men as the sample group. Blood samples from the individuals are grouped as prostate cancer and BPH (benign prostatic hyperplasia) groups. 27 prostate cancer patients whom some of them also operated are assembled in the patients group and the other 32 individuals are grouped as BPH group. Micro RNA expression levels evaluated by RT-PCR. Results: Prostate cancer group when compared with the control group, it is observed that expression levels of miRNA-221 and miRNA-432 increased while expression levels of miRNA-17-5p, miRNA-30c, miRNA-107, miRNA-141, miRNA-145, miRNA-181a-2, miRNA-331-3p, miRNA-574-3p decreased and expression levels of miRNA-21 and miRNA-375 are quite similar between the groups. Conclusion: The prospect of strong and sensitive serum miRNA expression levels in prostate cancer cases which are easily detectable by non-invasive methods as biomarkers is a promising field of study. Nevertheless, it is currently necessary to work in conjunction with both tissue and serum to enhance both sensitivity and specificity of miRNAs as biomarkers. As such, expression levels of the same miRNAs in tissue and serum provide different expression values which in turn make it difficult to indicate a common biomarker.


2021 ◽  
Vol 22 (3) ◽  
pp. 1007
Author(s):  
Jaehoon Lee ◽  
Hee Seung Lee ◽  
Soo Been Park ◽  
Chanyang Kim ◽  
Kahee Kim ◽  
...  

Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.


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