The Current Status of Kidney Cancer Urine Markers - A Systematic Review

BACKGROUND: Renal cell carcinoma is the 9th most common malignant disease in the Western World. Typically, patients develop symptoms in a late stage of the disease and most of them are diagnosed by chance. Up to 30% of the patients at the time of diagnosis had metastatic disease. Therefore, highly specific and sensitive biomarkers for the detection and progression of kidney cancer are of great importance. Here, urine markers can be a major advantage and can have a huge clinical impact on the diagnosis, differentiation and prognosis of kidney cancer. At the moment there are several approaches to improve these conditions. METHODS: Asystematic literature research was performed according to the PRISMA guidelines to identify studies reporting urine markers for kidney cancer between 2012 and 2021. A two-step process for the selection of the studies was initiated. In total 287 studies were considering for the final analysis. In total, 6 studies, which presented potential urinary biomarker were analyzed in depth. RESULTS: The major focus was on urinary markers for the detection, progression and differentiation of renal cell carcinoma. In total, a study population of 1099 patients were investigated in the different studies that were analyzed in depth. The median patient sample size of the different studies was 157 patients. The focus was based on the investigation of different microRNAs and proteins as urinary marker for kidney cancer detection. CONCLUSION: Overall, there are different approaches present for the detection, prognosis and differentiation of kidney cancer in urine but most of the studies are based on a small sample size and need to be validated in a greater collective. Furthermore, the standard should be improved to bring these biomarkers into routine clinical practice

Predictors for Outcome and Complications Related to Urinary Diversion

Background/Aim: Predictors for complications such as insufficiency of intestinal anastomosis in urinary diversion and other risk factors are not well defined. We aimed to elucidate predictive factors for complications in urinary diversions based on preoperative comorbidities and major complications. A special focus was set on anastomosis insufficiency as a major complication. Patients and Methods: Preoperative comorbidities, postoperative complications, duration of hospital stay, and follow-up were analyzed in 317 patients with urinary diversion. The impact of preoperative comorbidities on diversion types was described and quantified as defined by the age-adjusted Charlson Comorbidity Index. Results: Overall, 14.8% of patients showed anastomosis-related complications, most within the ileal conduit group (15.9% in the cohort). Severe complications (Clavien-Dindo Classification Score >IIIa) were found in smokers (p=0.046), and in patients with vascular diseases (p=0.007), a high American Society of Anaesthesiologists (ASA)-score (p=0.047), a R1-(p=0.009), as well as a pN1 (p=0.007) status. Conclusion: Several independent predictors for several postoperative complications in urinary diversions were identified, which were independent of the diversion method

Vimentin 3 Expression in Prostate Cancer Cells

Background/Aim: Vimentin3 (Vim3) was recently described as a tumour marker for the direct discrimination between benign and malignant kidney tumours. Here, we examined its expression in prostate cancer (PCa) cell lines and the regulation of its expression by endothelin receptors. Materials and Methods: Prostate cancer cell lines (PC3, DU145, LNCap) were incubated with endothelin 1 (ET-1), BQ123 [endothelin A receptor (ETAR) antagonist], BQ788 [endothelin B receptor (ETBR) antagonist), BQ123+ET-1, BQ788+ET-1 for 24 h and a scratch assay was performed. Cell extracts were analysed by western blotting and qRT-PCR. Results: ET-1 induced Vim3 overexpression. Blocking the ETBR in the different prostate cancer cell lines yielded a higher migration rate, whereby Vim3 expression was significantly increased. Conclusion: Vim3 concentration increases in cell lines without a functional ETBR and may be used as a marker for PCas where ETBR is frequently methylated

The combination of microRNA-371a-3p and 375-5p can distinguish viable germ cell tumor and teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens

Background: To identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic germ cell tumor (GCT) patients with residual masses >= 1 cm after chemotherapy. Biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N. Methods: We selected 48 metastatic GCT patients who had undergone pcRPLND. V, pure T and N was shown in the resected tissue of 16 patients, respectively. Of these areas total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T vs. N. Results: On comparing V vs. N miR-371a-3p achieved the highest fold change (FC) of 31.1 (P=0.023) while for T vs. N miR-375-5p performed best (FC 64.2; P<0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3. Conclusions: By combining miR-371a-3p and miR-375-5p in pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient's serum are needed to confirm the clinical impact of these biomarkers

Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

Introduction: The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. Methods: We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. Results: Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, p = 0.031), visceral metastases (58 vs. 32%, p = 0.015), and poor prognosis (p = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, p = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, p = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (p = 0.049) during a median follow-up of 36 months (10-115.5). Conclusions: The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients

COVID-19 Infection Induce miR-371a-3p Upregulation Resulting in Influence on Male Fertility

In December 2019, the first case of COVID-19 was reported and since then several groups have already published that the virus can be present in the testis. To study the influence of SARSCoV-2 which cause a dysregulation of the androgen receptor (AR) level, thereby leading to fertility problems and inducing germ cell testicular changes in patients after the infection. Formalin-Fixed-Paraffin-Embedded (FFPE) testicular samples from patients who died with or as a result of COVID-19 (n = 32) with controls (n = 6), inflammatory changes (n = 9), seminoma with/without metastasis (n = 11) compared with healthy biopsy samples (n = 3) were analyzed and compared via qRT-PCR for the expression of miR-371a-3p. An immunohistochemical analysis (IHC) and ELISA were performed in order to highlight the miR-371a-3p targeting the AR. Serum samples of patients with mild or severe COVID-19 symptoms (n = 34) were analyzed for miR-371a-3p expression. In 70% of the analyzed postmortem testicular tissue samples, a significant upregulation of the miR-371a-3p was detected, and 75% of the samples showed a reduced spermatogenesis. In serum samples, the upregulation of the miR-371a-3p was also detectable. The upregulation of the miR-371a-3p is responsible for the downregulation of the AR in SARS-CoV-2-positive patients, resulting in decreased spermatogenesis. Since the dysregulation of the AR is associated with infertility, further studies have to confirm if the identified dysregulation is regressive after a declining infection

COVID-19 Infection Induce miR-371a-3p Upregulation Resulting in Influence on Male Fertility

In December 2019, the first case of COVID-19 was reported and since then several groups have already published that the virus can be present in the testis. To study the influence of SARS-CoV-2 which cause a dysregulation of the androgen receptor (AR) level, thereby leading to fertility problems and inducing germ cell testicular changes in patients after the infection. Formalin-Fixed-Paraffin-Embedded (FFPE) testicular samples from patients who died with or as a result of COVID-19 (n = 32) with controls (n = 6), inflammatory changes (n = 9), seminoma with/without metastasis (n = 11) compared with healthy biopsy samples (n = 3) were analyzed and compared via qRT-PCR for the expression of miR-371a-3p. An immunohistochemical analysis (IHC) and ELISA were performed in order to highlight the miR-371a-3p targeting the AR. Serum samples of patients with mild or severe COVID-19 symptoms (n = 34) were analyzed for miR-371a-3p expression. In 70% of the analyzed postmortem testicular tissue samples, a significant upregulation of the miR-371a-3p was detected, and 75% of the samples showed a reduced spermatogenesis. In serum samples, the upregulation of the miR-371a-3p was also detectable. The upregulation of the miR-371a-3p is responsible for the downregulation of the AR in SARS-CoV-2-positive patients, resulting in decreased spermatogenesis. Since the dysregulation of the AR is associated with infertility, further studies have to confirm if the identified dysregulation is regressive after a declining infection