Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Testicular cancer is an important disease with increasing incidence and a high burden of morbidity and mortality in young men worldwide. Histological examination of the testicular tissue after orchiectomy plays an important role alongside patient history, imaging, clinical presentation and laboratory parameters. Surgical procedures and chemotherapeutic treatment provide a high chance of cure in early stages, though some patients in advanced stages belonging to a poor risk group experience cancer-related death. Though conventional serum-based tumor markers, including α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are useful as prognostic and diagnostic biomarkers, unfortunately, these tumor markers only have a sensitivity of about 60%, and in pure seminoma even lower with about 20%. Therefore, the development of new tumor markers is an important and intensively ongoing issue. The analysis of epigenetic modification and non-coding RNA microRNAs (miRNAs) are carrying most promising potential as tumor markers in future. miRNAs are small RNAs secreted by testicular tumor cells and circulate and be measurable in body fluids. In recent years, miRNAs of the miR-371-373 cluster in particular have been identified as potentially superior tumor markers in testicular cancer patients. Studies showed that miR-371a-3p and miR-302/367 expression significantly differ between testicular tumors and healthy testicular tissue. Several studies including high prospective multi-center trials clearly demonstrated that these miRNAs significantly exceed the sensitivity and specificity of conventional tumor markers and may help to facilitate the diagnosis, follow-up, and early detection of recurrences in testicular cancer patients. In addition, other miRNAs such as miR-223-3p, miR-449, miR-383, miR-514a-3p, miR-199a-3p, and miR-214 will be discussed in this review. However, further studies are needed to identify the value of these novel markers in additional clinical scenarios, including the monitoring in active surveillance or after adjuvant chemotherapy, but also to show the limitations of these tumor markers. The aim of this review is to give an overview on the current knowledge regarding the relevance of non-coding miRNAs as biomarkers in testicular cancer.

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Insulin-like factor 3, luteinizing hormone and testosterone in testicular cancer patients: effects of β-hCG and cancer treatment

Andrology ◽

10.1111/andr.12581 ◽

2019 ◽

Vol 7 (4) ◽

pp. 441-448 ◽

Cited By ~ 3

Author(s):

L. C. Steggink ◽

A. P. van Beek ◽

H. Boer ◽

C. Meijer ◽

S. Lubberts ◽

...

Keyword(s):

Luteinizing Hormone ◽

Testicular Cancer ◽

Cancer Treatment ◽

Cancer Patients ◽

Β Hcg

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Pre-orchiectomy serum tumor markers as a predictor of recurrence in stage I germ cell tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.389 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 389-389

Author(s):

Rohit R Badia ◽

Rashed Ghandour ◽

Jeffrey Howard ◽

Joseph G Cheaib ◽

Ragheed Saoud ◽

...

Keyword(s):

Testicular Cancer ◽

Cancer Patients ◽

Tumor Markers ◽

Germ Cell Tumors ◽

Standard Of Care ◽

Stage I ◽

Testis Cancer ◽

Serum Tumor Markers ◽

Kaplan Meier ◽

Stage Ia

389 Background: Organ confined (stage IA/IB) testicular cancer has a high cure rate regardless of initial treatment modality, making it important to weigh the toxicities of treatment against potential benefits. While many clinicians routinely obtain serum tumor markers (STMs) prior to radical orchiectomy, their role in predicting recurrence in stage IA and IB testicular cancer has not been studied. Methods: A multi-institutional database of stage I testicular cancer patients diagnosed between 2006 and 2018 was created. Univariate and multivariate regression models were created to understand which factors predict recurrence. Recurrence analyses using Kaplan-Meier curves for elevated and normal pre-orchiectomy STMs were also generated. Results: 150 patients met the study criteria, of whom 16 (11%) relapsed (Table). 9 (56%) patients with recurrence had elevated pre-orchiectomy STMs, and 7 (44%) had normal pre-orchiectomy STMs. Similarly, 75 patients (56%) without relapse had elevated pre-orchiectomy STMs. Of 9 patients with elevated pre-orchiectomy STMs, 6 (67%) had normal STMs at recurrence; of 7 with normal pre-orchiectomy STMs, 4 patients (57%) had elevated STMs at recurrence. On Kaplan-Meier analysis, no association between level of pre-orchiectomy STMs and recurrence free survival was observed. Conclusions: Pre-orchiectomy STMs were not independently associated with recurrence in stage I testis cancer. Interestingly, there was also no association between positivity of pre-orchiectomy STMs and whether or not STMs were elevated at recurrence. These findings support the continued use of standard-of-care imaging and STMs in surveillance of stage IA/IB testicular cancer patients regardless of pre-orchiectomy STMs. [Table: see text]

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Clinical impact of PTEN methylation status as a prognostic marker for breast cancer

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00169-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Amal Ramadan ◽

Maha Hashim ◽

Amr Abouzid ◽

Menha Swellam

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Markers ◽

Prognostic Marker ◽

Methylation Status ◽

Clinical Impact ◽

Breast Cancer Patients ◽

Duct Carcinoma ◽

Cancer Group ◽

And Control

Abstract Background Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0–I, n = 48) and late stage (II–III, n = 64), and graded into low grade (I–II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. Results The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. Conclusions PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.

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DNA Flow Cytometry in Sperm Cells from Testicular Cancer Patients

European Urology ◽

10.1159/000473600 ◽

1991 ◽

Vol 19 (2) ◽

pp. 125-131 ◽

Cited By ~ 2

Author(s):

S.D. Fosså ◽

J.E. Melvik ◽

N.O. Juul ◽

E.O. Pettersen ◽

Ø. Åmellem ◽

...

Keyword(s):

Flow Cytometry ◽

Testicular Cancer ◽

Cancer Patients ◽

Dna Flow Cytometry ◽

Sperm Cells

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Tumor Markers in Advanced Nonseminomatous Testicular Cancer

The Journal of Urology ◽

10.1016/s0022-5347(17)54073-2 ◽

1982 ◽

Vol 127 (4) ◽

pp. 834-834

Author(s):

G.J. Bosl ◽

P.H. Lange ◽

L.E. Nochomovitz ◽

A. Goldmann ◽

E.E. Fraley ◽

...

Keyword(s):

Testicular Cancer ◽

Tumor Markers

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Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients

Human Reproduction ◽

10.1093/humrep/del167 ◽

2006 ◽

Vol 21 (11) ◽

pp. 2882-2889 ◽

Cited By ~ 84

Author(s):

Loredana Gandini ◽

Paolo Sgrò ◽

Francesco Lombardo ◽

Donatella Paoli ◽

Franco Culasso ◽

...

Keyword(s):

Testicular Cancer ◽

Cancer Patients ◽

Sperm Parameters

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Epigenetic Mechanism and Survival Prognosis Analysis of Serum Exosomes from Ovarian Cancer Patients based on Sequencing Technology and Bioinformatics

10.21203/rs.3.rs-981954/v1 ◽

2021 ◽

Author(s):

Li Xia ◽

Huang He

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Target Genes ◽

Epigenetic Modification ◽

Gene Prediction ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Survival Prognosis ◽

Signaling Axis ◽

Serum Exosomes

Abstract Backguound: To screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, in depth study of the potential mechanism of action of ovarian cancer, prediction of potential therapeutic targets and survival prognosis analysis of potential targets.Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients as the control group, and whole transcriptome of serum exosomes was performed to obtain differentially expressed lncRNA and mRNA in ovarian cancer,The miRcode database and miRNA target gene prediction website were used to predict the target genes, Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and the R language was used for GO and KEGG enrichment analysis of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival。Results: A total of 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining mircode database and miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4), and survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10 only genes, but not for the other genes, and through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor - activated receptor activity, and GABA receptor binding, and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, tyrosine stimulation to EGFR in signaling pathways such as resistance to enzyme inhibitors.Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.

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