scholarly journals The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 535
Author(s):  
Anouk E. Hentschel ◽  
Rianne van den Helder ◽  
Nienke E. van Trommel ◽  
Annina P. van Splunter ◽  
Robert A. A. van Boerdonk ◽  
...  

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Long Yang ◽  
Yan-Lei Li ◽  
Xiao-Qing Li ◽  
Zheng Zhang

Purpose. To compare the expression level of apelin in muscle-invasive bladder cancer and matched paracarcinoma tissues and investigate the relationship between apelin and clinical prognosis in the patients. Methods. To assess apelin expression by using immunohistochemical method compared with bladder tumors and matched paracarcinoma tissues. Subsequently, the correlation of apelin expression with the clinicopathological features of bladder cancer patients was analyzed. Kaplan-Meier survival curves method was used to analyze apelin prognostic significance for muscle-invasive bladder cancer patients (including 404 muscle-invasive bladder cancer patients and 28 normal bladder tissues, in TCGA dataset). Results. Apelin protein level was overexpressed in bladder tumor tissues compared with paracarcinoma tissues. Furthermore, high apelin expression was associated with high tumor stage (P<0.05), distant metastasis (P<0.05), and vascular invasion (P<0.05). Kaplan-Meier curve analyses showed that the overexpression of apelin was a potential predictor of overall survival and disease-free survival. Conclusion. Apelin was upregulated in bladder tumor tissues compared with matched adjacent noncancer tissues, especially in the high tumor stage, distant metastasis, and vascular invasion. What is more, high expression of apelin in muscle-invasive bladder cancer indicates the poor prognosis. These data suggested that apelin might be a therapeutic potential biomarker in muscle-invasive bladder cancer patients.


2021 ◽  
Vol 20 ◽  
pp. 153303382110391
Author(s):  
Zhijia Zhang ◽  
Yanxia Sang ◽  
Zhengan Liu ◽  
Jinkai Shao

Objective: Our study aimed to evaluate the correlation of circular RNA SMARCA5 (circ-SMARCA5) and microRNA 432 (miR-432) with clinical characteristics and survival in bladder cancer patients. Methods: Preoperative clinicopathologic features and survival data of 156 bladder cancer patients were retrospectively reviewed. A total of 156 cases of tumor tissues, whereas 71 cases out of 156 available adjacent tissues were obtained from the Pathology Department for circ-SMARCA5 and miR-432 detections using real-time quantitative polymerase chain reaction. Results: Circ-SMARCA5 was upregulated but miR-432 was downregulated in tumor tissues compared with adjacent tissues; meanwhile, circ-SMARCA5 expression was negatively correlated with miR-432 in bladder cancer tissues. Circ-SMARCA5 high expression was correlated with larger tumor size, higher tumor stage, and lymph node (LYN) metastasis. However, miR-432 high expression was correlated with single multiplicity, smaller tumor size, lower tumor stage, less LYN metastasis in bladder cancer patients. Regarding survival, circ-SMARCA5 high expression was correlated with shorter disease-free survival (DFS) and overall survival (OS); whereas, miR-432 high expression was correlated with longer DFS and OS in bladder cancer patients. Further multivariate Cox's regression analysis displayed that circ-SMARCA5 high expression was an independent predictive factor for both worse DFS and OS in bladder cancer patients. Conclusion: Circ-SMARCA5 high expression but miR-432 low expression is correlated with advanced tumor features and poor survival of bladder cancer patients, which present as potential prognostic markers in bladder cancer.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 745-745
Author(s):  
Fumiaki Watanabe ◽  
Koichi Suzuki ◽  
Toshiki Rikiyama

745 Background: KRAS monitoringprovides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRASmutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in plasma by KRAS monitoringmay be even more valuablein pancreatic cancerpatients. In this study, we elucidated the clinicalsignificance of KRASmonitoring in pancreatic cancer patients during treatment. Methods: KRASin tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 83 patients with pancreatic tumors. KRASin plasma was analyzed for mutations(G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 88 patients who underwent the curative surgery (N = 45) or the chemotherapy (N = 33) and who had KRAS mutation in their tissues. Results: KRASmutation in tumor tissues was detected in 74 of 83 patients (89.2%). These 74 patients showed significantly poorer prognosis (MST; 32) than the seven patients without mutation (p = 0.03), whose MST were 193. Monitoring of KRASin plasma revealed KRASmutation in 35 of 88 patients (39.8%). In patients who underwent the chemotherapy (N = 33), 2years OS of patients who detected KRASmutation in plasma (N = 23) was 16.4% and them which not detected it (N = 10) was 53.3% (p = 0.18). But in the curative resection group (N = 45), 3years OS of patients who detected KRASmutation in plasma (N = 12) was 16.7% and them which not detected it (N = 33) was 68.2% (p = 0.00). Conclusions: KRASmutation in tissue and plasma could be a valuable predictive and prognostic biomarker in pancreatic cancer patients.


2021 ◽  
Vol 22 (4) ◽  
pp. 1713
Author(s):  
Xuan-Mei Piao ◽  
Eun-Jong Cha ◽  
Seok Joong Yun ◽  
Wun-Jae Kim

Bladder cancer (BCa) is the most prevalent neoplasia of the urinary tract. Unfortunately, limited improvements in effective BCa management have meant that it remains a challenging disease. Cystoscopy has been the gold standard for BCa diagnosis and surveillance for over two centuries but is an invasive and expensive approach. Recently, liquid biopsy has been identified as a promising field of cancer research, due to its noninvasiveness and ease of sampling. Liquid biopsy samples could provide comprehensive information regarding the genetic landscape of cancer and could track genomic evolution of the disease over time. Exosomes, which contain RNAs, DNAs, and proteins, are a potential source of tumor biomarkers in liquid biopsy samples. In particular, exosomal miRNAs (exomiRs) hold great promise as biomarkers for tumor development and progression. In this review, we provide an overview of liquid biopsy biomarkers, with a particular focus on the use of exomiRs as biomarkers of cancer, and summarize their clinical implications for BCa. Finally, we discuss the future perspectives of these biomarkers in cancer research.


2020 ◽  
Author(s):  
Carmen Rubio Alarcón ◽  
Dave E. van der Kruijssen ◽  
Lana Meiqari ◽  
Linda J. Bosch ◽  
John K. Simmons ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2004
Author(s):  
Qun Wang ◽  
Elisa Schmoeckel ◽  
Bernd P. Kost ◽  
Christina Kuhn ◽  
Aurelia Vattai ◽  
...  

The chemokine CCL22 recruits regulatory T (T-reg) cells into tumor tissues and is expressed in many human tumors. However, the prognostic role of CCL22 in cervical cancer (CC) has not been determined. This study retrospectively analyzed the clinical significance of the expression of CCL22 and FOXP3 in 230 cervical cancer patients. Immunohistochemical staining analyses of CCL22 and FOXP3 were performed with a tissue microarray. Double immunofluorescence staining, cell coculture, and ELISA were used to determine CCL22 expressing cells and mechanisms. The higher number of infiltrating CCL22+ cells (CCL22high) group was associated with lymph node metastasis (p = 0.004), Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stages (p = 0.010), therapeutic strategies (p = 0.007), and survival status (p = 0.002). The number of infiltrating CCL22+ cells was positively correlated with that of infiltrating FOXP3+ cells (r = 0.210, p = 0.001). The CCL22high group had a lower overall survival rate (OS), compared to the CCL22low group (p = 0.001). However, no significant differences in progression free survival (PFS) were noted between the two groups. CCL22high was an independent predictor of shorter OS (HR, 4.985; p = 0.0001). The OS of the combination group CCL22highFOXP3high was significantly lower than that of the combination group CCL22lowFOXP3low regardless of the FIGO stage and disease subtype. CCL22highFOXP3high was an independent indictor of shorter OS (HR, 5.284; p = 0.009). The PFS of group CCL22highFOXP3high was significantly lower than that of group CCL22lowFOXP3low in cervical adenocarcinoma, but CCL22highFOXP3high was not an independent indicator (HR, 3.018; p = 0.068). CCL22 was primarily expressed in M2-like macrophages in CC and induced by cervical cancer cells. The findings of our study indicate that cervical cancer patients with elevated CCL22+ infiltrating cells require more aggressive treatment. Moreover, the results provide a basis for subsequent, comprehensive studies to advance the design of immunotherapy for cervical cancer.


2018 ◽  
Vol 19 (9) ◽  
pp. 2514 ◽  
Author(s):  
Iris Lodewijk ◽  
Marta Dueñas ◽  
Carolina Rubio ◽  
Ester Munera-Maravilla ◽  
Cristina Segovia ◽  
...  

Bladder Cancer (BC) represents a clinical and social challenge due to its high incidence and recurrence rates, as well as the limited advances in effective disease management. Currently, a combination of cytology and cystoscopy is the routinely used methodology for diagnosis, prognosis and disease surveillance. However, both the poor sensitivity of cytology tests as well as the high invasiveness and big variation in tumour stage and grade interpretation using cystoscopy, emphasizes the urgent need for improvements in BC clinical guidance. Liquid biopsy represents a new non-invasive approach that has been extensively studied over the last decade and holds great promise. Even though its clinical use is still compromised, multiple studies have recently focused on the potential application of biomarkers in liquid biopsies for BC, including circulating tumour cells and DNA, RNAs, proteins and peptides, metabolites and extracellular vesicles. In this review, we summarize the present knowledge on the different types of biomarkers, their potential use in liquid biopsy and clinical applications in BC.


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