A Rare Case of Massive and Obstructive Colonic Metastasis of Bladder Urothelial Carcinoma

High expression of polo-like kinase 1 is associated with the metastasis and recurrence in urothelial carcinoma of bladder

Cutaneous metastases from urothelial carcinoma of the bladder are a rare disease. In previous reports, the most common metastatic cutaneous lesions were non-tender nodules on the abdominal skin. We report a patient with bladder urothelial carcinoma with cutaneous metastases initially presenting as right leg and suprapubic lymphedema. Bladder tumor was the incidental finding by magnetic resonance venography. Urothelial carcinoma (clinical stage IV) was diagnosed, and chemotherapy was performed. Extensive painful erythematous plaques with an erysipelas-like appearance located on the suprapubic area, chest and abdomen were noted, and cutaneous metastases were confirmed by histopathology. Subsequently, extensive scrotal and prepuce ulcerative changes developed. This paper reports a rare case of extensive cutaneous metastasis of bladder urothelial carcinoma who presented an interesting clinical course.

Screening and identification of potential prognostic biomarkers in bladder urothelial carcinoma: Evidence from bioinformatics analysis

Objective To detect the expression of metastasis- associated protein 1 (MTA- 1) and Ezrin in bladder urothelial carcinoma (BUC) and normal bladder mucosa, and to investigate their correlation with clinical pathology and prognosis. Methods The expression of MTA- 1 and Ezrin proteins was detected in 65 specimens of surgically resected BUC tissue and 30 of normal bladder mucosa with immunohistochemistry. The correlation of MTA- 1 and Ezrin expressions in BUC with clinicopathological parameters, the correlation between MTA-1 and Ezrin protein expressions and their effects on prognosis were also analyzed. Results In 65 specimens of BUC tissue, the positive rates of MTA- 1 and Ezrin expression were 72.3% (n=47) and 89.2% (n=58) , respectively, in contrast to 0% for both MTA- 1 and Ezrin expressions in 30 specimens of normal bladder mucosa, which reached the level of statistical difference (all P＜0.01). The expression of MTA- 1 in BUC tissue was closely related to the clinical stages, tumor pathological grading, metastasis and recurrence (all P＜0.01 ) , while the expression of Ezrin was closely related to the clinical stages, metastasis and recurrence (all P＜0.01 ), and the expression of MTA-1 was positively correlated with Ezrin expression (r=0.742, P＜0.01 ). The disease free survival (DFS) in patients with combined expression was significantly lower than that in those with negative expression of MTA- 1 and Ezrin (P＜0.01). Conclusion The high expression of MTA-1 and Ezrin is related to the occurrence,progression, as well as invasion and metastasis of BUC. Key words: Bladder neoplasms; Pathology, clinical; Immunohistochemistry; Tumor metastatic process-associated protein

Objective To investigate the expression of Snail in bladder urothelial carcinoma and evaluate its relationship with E-cadherin and a subset of T cell groups.Methods Immunohistochemical method was used to detect the expression of Snail and E-cadherin proteins in tissue from 156 cases of bladder urothelial carcinoma and 80 cases of the para-cancerous mucosa. The proteins expression status was analyzed with clinico-pathological data. Meanwhile, correlations with Snail and CD4+, CD8+, CD4+/CD8+ were analyzed.Results The positive rate of Snail in bladder urothelial carcinoma was 65.4％ , which was significantly higher than that in para-cancerous mucosa (48.8％). The expression of Snail was significantly correlated with the clinical stage, pathological grade, tumor quantity, distant metastasis and tumor recurrence.There was negative correlation between the expression of Snail and E-cadherin in bladder urothelial carcinoma. Positive expression of Snail had a negative correlation with the number of CD4+ and CD4+/CD8+ , whereas it had no significant correlation with the number of CD8+.Conclusions By inhibition of the E-cadherin expression and inducing local immunosuppression, Snail might play an important role in the process of the invasion and metastasis of bladder urothelial carcinoma. Key words: Snail protein; E-cadherin protein; Bladder urothelial carcinoma; Subset of Tcell; Immunohistochemistry

Background: Bladder urothelial carcinoma (BLCA) is a prevalent malignant tumor known for its high recurrence rates and limited therapeutic efficacy. Cellular senescence has been extensively shown to inhibit tumorigenesis via cell cycle arrest. Consequently, the identification of senescence-associated biomarkers is essential for enhancing the diagnosis, prognosis, and immunotherapeutic outcomes of BLCA.Method: This study integrated the TCGA-BLCA and GSE13507 datasets to analyze senescence-related genes. ConsensusClusterPlus was employed for cluster analysis, while immune infiltration was assessed using CIBERSORT. A diagnostic and prognostic model for BLCA was developed and validated through the combination of various machine learning algorithms. Experimental validation was conducted using qRT-PCR, colony formation, and Transwell assays to evaluate the functional role of PAQR4.Result: Our study revealed that aging-related samples demonstrated improved survival rates and a lower incidence of high-grade tumors. Cluster analysis identified two distinct subgroups of BLCA characterized by unique immune infiltration profiles and varying responses to immune checkpoint blockade. The diagnostic and prognostic models developed from aging-related genes were subsequently validated. Notably, PAQR4 was identified as a critical aging-related gene linked to poor prognosis and an immunosuppressive microenvironment. The knockdown of PAQR4 significantly inhibited the proliferation and metastasis of BLCA cells.Conclusion: PAQR4 is a novel biomarker and therapeutic target for BLCA, influencing cellular senescence, immune evasion, and metastasis. This study provides insights into the senescence-related mechanisms and offers tools for precision diagnosis and the optimization of immunotherapy in BLCA.

A potential role for 6-sulfo sialyl Lewis X in metastasis of bladder urothelial carcinoma

Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well.Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level.Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines.Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA.

The main route of metastasis of bladder urothelial carcinoma is through lymph nodes; however, its exact mechanism remains unclear. In this study, we found an association of nucleolar and spindle associated protein 1 (NUSAP1) expression with BUC tissues along with lymph node metastasis and the survival prognosis. A total of 178 pathological specimens following radical bladder cancer resection were obtained. NUSAP1 expression was analyzed by immunohistochemistry. We evaluated the correlation between clinicopathological characteristics and NUSAP1 expression. Logistic regression was used to determine the independent variables that influenced lymph node metastasis. Uni- and multi-factorial Cox regression methods were used to determine the prognostic value of NUSAP1 expression in urothelial carcinoma of the bladder. High expression of NUSAP1 in BUC was not significantly related to the patient’s gender, age, or tumor number (p > 0.05), however was significantly associated with pathological grade, tumor diameter, pathological stage, and lymph node metastasis (p < 0.05). Lymph node metastasis was significantly correlated with pathological stage, pathological grade, tumor number, tumor diameter, and NUSAP1 expression (p < 0.05); only NUSAP1 expression was an independent predictor of lymph node metastasis in BUC (OR:1.786, 95% CI 1.229–2.596, p = 0.002). In addition, high NUSAP1 expression was an independent prognostic predictor for BUC. In BUC, NUSAP1 showed high expression and was significantly associated with lymph node metastasis, pathological stage, pathological grade, and tumor diameter. NUSAP1 was an independent predictor of lymph node metastasis and prognosis in BUC; higher expression indicated poorer prognosis of BUC patients.

Bladder urothelial carcinoma is a malignant tumor with a high incidence in the uropoietic system. Considerable studies have shown that long noncoding RNA (lncRNA) plays an important role in the development and progression of bladder urothelial carcinoma. In this study, the lncRNA expression and clinical data of 377 bladder urothelial carcinoma patients were obtained from The Cancer Genome Atlas database and differentially expressed lncRNAs in cancer and normal groups were evaluated. Univariate COX and multivariate COX regression analyses of prognosis were performed on differentially expressed lncRNAs in the training data sets, six prognosis-related lncRNAs (LINC02195, LINC01484, LINC01468, SMC2-AS1, AC011298.1, and PTPRD-AS1) were assessed, and a six-lncRNA signature was constructed. The predictive capability of this six-lncRNA signature was validated in the testing data sets and entire data sets. The prognostic ability of the six-lncRNA signature was independent of other clinical elements after multivariate COX regression and stratified analyses of with other clinical elements. We performed functional enrichment analysis with the six prognosis-related lncRNAs. Results of functional enrichment revealed that these prognosis-related lncRNAs might promote the development and metastasis of bladder urothelial carcinoma. In summary, the six-lncRNA signature that we developed could effectively predict the prognosis of bladder urothelial carcinoma patients. This six-lncRNA signature might be a novel independent prognostic marker of bladder urothelial carcinoma. Moreover, it also provides novel insights into the mechanism of bladder urothelial carcinoma.

ObjectiveTo observe the expression of hypoxia inducible factor-1α (HIF-1α) in bladder urothelial carcinoma (BUC) and the relationship between it with the metastasis of BUC.MethodsExpression of HIF-1α was detected by SP immunohistochemistry in BUC, to find the relationship of HIF-1α with the clinical pathological characteristics and lymph node metastasis of BUC patientsResultsThe positive expression rate of HIF-1α was 75.6% in 90 cases with BUC (68/90), the positive expression rate in 30 cases of normal bladder tissue cells is 6.7% (2/30), compare the two groups, there was a significant difference between their expression (P<0.01). In different pathological grading and clinical staging, and also in lymph node metastasis, its expressive discrepancy was statistically significant (P<0.05)ConclusionsThe HIF-1 α protein of BUC patients with abnormal high expression is closely related to the cancer growth, suggesting that the protein can be used as an important molecular biological behavior and prognosis judgement of BUC cell markers, also has some clinical reference value in the treatment of postoperative follow-up guidance.

Heart metastases from urothelial carcinoma of the bladder have rarely been reported in the literature. We present a case complicated by symptomatic disseminated intravascular coagulation in a 67-year-old woman. A rapid and sustained recovery from hemostatic troubles was obtained following fibrinogen supplementation combined with second-line paclitaxel chemotherapy.

Vaginal metastases from urothelial cancer are a rare entity and in literature, few cases are described. We report a case of a 68 year-old woman with history of bladder urothelial carcinoma underwent to radical cystectomy who came in our department after 5 months for pelvic pain and vaginal bleeding. Objective examination revealed an ulcerative, solid vaginal lesion in the upper vaginal wall. We performed a vaginal biopsy that showed urothelial carcinoma compatible with the primitive bladder cancer. The patient underwent to surgery and was sent to oncological evaluation.

Metastatic disease to the thyroid is a very uncommon situation. The cancers that usually metastasize to the thyroid include the breast, lung, colon and kidney. To our knowledge, metastasis from the bladder to the thyroid is exceedingly rare. Here, we report a case of a unique metastatic transitional cell carcinoma to the thyroid gland three years after total cystectomy.

Cutaneous metastasis of bladder urothelial carcinoma; A rare conditions