Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups

Aim and Objective: Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). Materials and Methods: RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October of 2019 in China. Results: The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5 ), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020–1.077, p = 0.001). Conclusions: Increased FADS1 expression in bladder cancer is associated with advanced clinical pathological features and may be a potential biomarker for poor prognosis.

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Hybrid ileal pouch with concomitant anti-refluxing and refluxing ureteroileal anastomosis

BMC Urology ◽

10.1186/s12894-021-00828-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Se Young Choi ◽

Bumjin Lim ◽

Byung Hoon Chi ◽

Jung Hoon Kim ◽

Wonchul Lee ◽

...

Keyword(s):

Bladder Cancer ◽

Renal Function ◽

Postoperative Complications ◽

Functional Outcomes ◽

Ileal Pouch ◽

Oncologic Outcomes ◽

Voiding Function ◽

Short Bowel ◽

Left And Right ◽

Grade 3

Abstract Purpose We report our preliminary experience of using a hybrid ileal pouch, assessing oncologic outcomes, complications, voiding, and renal function. Methods The study included 25 patients with bladder cancer treated with radical cystectomy with a hybrid ileal pouch with concomitant anti-refluxing and refluxing anastomosis, performed by a single surgeon. The patients were divided into two groups (first and last cases) according to the surgery date. Postoperative complications, separate renal function by renal scan, voiding function by uroflowmetry with residual urine, and oncologic outcomes were assessed. Results The surgery duration was shorter in the last cases than the first cases. The voiding volume increased with time. There were 23 cases of grade 3 complication in 12 patients and one case of grade 4 complication (sepsis). In the first cases, ureterovesical stenosis occurred in five cases, whereas in the last cases, there were no cases of stenosis. In separate renal function, there was no difference between the left and right side or between the first and last cases. Conclusions The hybrid ileal pouch showed acceptable oncologic and functional outcomes and complications; therefore, it can be used according to the appropriate surgical situation with a relatively short bowel segment during neobladder construction.

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Cancer Grade Model: a multi-gene machine learning-based risk classification for improving prognosis in breast cancer

British Journal of Cancer ◽

10.1038/s41416-021-01455-1 ◽

2021 ◽

Author(s):

E. Amiri Souri ◽

A. Chenoweth ◽

A. Cheung ◽

S. N. Karagiannis ◽

S. Tsoka

Keyword(s):

Breast Cancer ◽

Machine Learning ◽

Clinical Decision Making ◽

Histological Grade ◽

Tumour Size ◽

Clinical Decision ◽

Gene Signature ◽

Risk Classification ◽

Breast Cancers ◽

Grade 3

Abstract Background Prognostic stratification of breast cancers remains a challenge to improve clinical decision making. We employ machine learning on breast cancer transcriptomics from multiple studies to link the expression of specific genes to histological grade and classify tumours into a more or less aggressive prognostic type. Materials and methods Microarray data of 5031 untreated breast tumours spanning 33 published datasets and corresponding clinical data were integrated. A machine learning model based on gradient boosted trees was trained on histological grade-1 and grade-3 samples. The resulting predictive model (Cancer Grade Model, CGM) was applied on samples of grade-2 and unknown-grade (3029) for prognostic risk classification. Results A 70-gene signature for assessing clinical risk was identified and was shown to be 90% accurate when tested on known histological-grade samples. The predictive framework was validated through survival analysis and showed robust prognostic performance. CGM was cross-referenced with existing genomic tests and demonstrated the competitive predictive power of tumour risk. Conclusions CGM is able to classify tumours into better-defined prognostic categories without employing information on tumour size, stage, or subgroups. The model offers means to improve prognosis and support the clinical decision and precision treatments, thereby potentially contributing to preventing underdiagnosis of high-risk tumours and minimising over-treatment of low-risk disease.

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RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing

Oncogene ◽

10.1038/s41388-021-01666-z ◽

2021 ◽

Author(s):

Qiuxia Yan ◽

Peng Zeng ◽

Xiuqin Zhou ◽

Xiaoying Zhao ◽

Runqiang Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Alternative Splicing ◽

Rna Binding ◽

Aerobic Glycolysis ◽

Histological Grade ◽

Migration And Invasion ◽

Binding Motif ◽

Hnrnp A1

AbstractThe prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progression remains unclear. In this study, we found that RBMX was significantly downregulated in BCa tissues, especially in muscle-invasive BCa tissues. RBMX expression was negatively correlated with tumor stage, histological grade and poor patient prognosis. Functional assays demonstrated that RBMX inhibited BCa cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. Mechanistic investigations revealed that hnRNP A1 was an RBMX-binding protein. RBMX competitively inhibited the combination of the RGG motif in hnRNP A1 and the sequences flanking PKM exon 9, leading to the formation of lower PKM2 and higher PKM1 levels, which attenuated the tumorigenicity and progression of BCa. Moreover, RBMX inhibited aerobic glycolysis through hnRNP A1-dependent PKM alternative splicing and counteracted the PKM2 overexpression-induced aggressive phenotype of the BCa cells. In conclusion, our findings indicate that RBMX suppresses BCa tumorigenicity and progression via an hnRNP A1-mediated PKM alternative splicing mechanism. RBMX may serve as a novel prognostic biomarker for clinical intervention in BCa.

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Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group

Cancers ◽

10.3390/cancers13081902 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1902

Author(s):

Luciana Caravatta ◽

Giovanna Mantello ◽

Francesca Valvo ◽

Pierfrancesco Franco ◽

Lucrezia Gasparini ◽

...

Keyword(s):

Cancer Patients ◽

Clinical Outcomes ◽

Anal Cancer ◽

Treatment Time ◽

Histological Grade ◽

Anal Carcinoma ◽

Nodal Involvement ◽

Free Survival ◽

Intensity Modulated ◽

Grade 3

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

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Lymph Node Metastasis in Patients With Endometrioid Endometrial Cancer: Overtreatment Is the Main Issue

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000937 ◽

2017 ◽

Vol 27 (4) ◽

pp. 748-753 ◽

Cited By ~ 8

Author(s):

Alper Karalok ◽

Taner Turan ◽

Derman Basaran ◽

Osman Turkmen ◽

Gunsu Comert Kimyon ◽

...

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Histological Grade ◽

Myometrial Invasion ◽

Lymph Node Involvement ◽

Node Metastasis ◽

Deep Myometrial Invasion ◽

Endometrioid Endometrial Cancer ◽

Grade 3

ObjectiveThe aim of this study was to evaluate the effectiveness of histological grade, depth of myometrial invasion, and tumor size to identify lymph node metastasis (LNM) in patients with endometrioid endometrial cancer (EC).MethodsA retrospective computerized database search was performed to identify patients who underwent comprehensive surgical staging for EC between January 1993 and December 2015. The inclusion criterion was endometrioid type EC limited to the uterine corpus. The associations between LNM and surgicopathological factors were evaluated by univariate and multivariate analyses.ResultsIn total, 368 patients were included. Fifty-five patients (14.9%) had LNM. Median tumor sizes were 4.5 cm (range, 0.7–13 cm) and 3.5 cm (range, 0.4–33.5 cm) in patients with and without LNM, respectively (P = 0.005). No LMN was detected in patients without myometrial invasion, whereas nodal spread was observed in 7.7% of patients with superficial myometrial invasion and in 22.6% of patients with deep myometrial invasion (P < 0.0001). Lymph node metastasis tended to be more frequent in patients with grade 3 disease compared with those with grade 1 or 2 disease (P = 0.131).ConclusionsThe risk of lymph node involvement was 30%, even in patients with the highest-risk uterine factors, that is, those who had tumors of greater than 2 cm, deep myometrial invasion, and grade 3 disease, indicating that 70% of these patients underwent unnecessary lymphatic dissection. A precise balance must be achieved between the desire to prevent unnecessary lymphadenectomy and the ability to diagnose LNM.

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LncRNA CASC2 Plays an Indicative Role in Diagnosing Bladder Cancer

10.21203/rs.3.rs-62220/v1 ◽

2020 ◽

Author(s):

Hao Zi ◽

Wen-Lin Tao ◽

Lei Gao ◽

Zhao-Hua Yu ◽

Xiao-Dong Bai ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Roc Curve ◽

Histological Grade ◽

Diagnostic Value ◽

Expression Level ◽

Chi Square ◽

Healthy Group ◽

Cancer Group ◽

Incidence And Mortality

Abstract Background: Bladder cancer is a common cancer of urinary system, with high incidence and mortality. LncRNA CASC2 as a tumor suppressor has been reported to be involved in many human tumors. In this study, we aimed to explore the diagnostic value of CASC2 for bladder cancer patients.Methods: qRT-PCR was used to detect the expression level of CASC2 in 140 bladder cancer patients and 90 healthy volunteers. The differences of CASC2 expression between the cancer group and healthy group were analyzed using student’s t test. The correlation of CASC2 expression with clinical characteristics of the bladder cancer patients was estimated with Chi-square test. In addition, ROC curve was plotted to evaluate the diagnostic value of CASC2 for bladder cancer patients.Results: Serum CASC2 level was lower in bladder cancer patients than that in healthy group (P<0.05). The expression level of CASC2 was significantly associated with histological grade (P=0.000), TNM stage (P=0.000), and lymph node metastasis (P=0.001). The area under the ROC curve (AUC) was 0.864 and the optimal cutoff value was 0.955, suggesting the diagnostic value of CASC2 for bladder cancer. The diagnostic sensitivity was 77.8% and specificity was 85.7%.Conclusion: CASC2 may be a novel biomarker for early diagnosis of bladder cancer.

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PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population

10.21203/rs.3.rs-84426/v1 ◽

2020 ◽

Author(s):

Shuangqing Cao ◽

Lei Zheng

Keyword(s):

Bladder Cancer ◽

Mrna Expression ◽

Cox Regression ◽

Histological Grade ◽

Tnm Stage ◽

Cox Regression Analysis ◽

Relative Expression ◽

Kaplan Meier ◽

Normal Bladder ◽

Cancer Tissues

Abstract Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.

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Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer

Cancers ◽

10.3390/cancers12102748 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2748

Author(s):

Manabu Kojima ◽

Kotaro Sugimoto ◽

Mizuko Tanaka ◽

Yuta Endo ◽

Hitomi Kato ◽

...

Keyword(s):

Endometrial Cancer ◽

Histological Grade ◽

Survival Rates ◽

Prognostic Significance ◽

Clinicopathological Parameters ◽

Intratumor Heterogeneity ◽

Aberrant Expression ◽

Independent Prognostic Marker ◽

Grade 3 ◽

Expression Score

Background: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. Results: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological type, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). Conclusions: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

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Neoadjuvant accelerated MVAC therapy in bladder cancer: toxicity and efficacy correlation

American Journal of BioMedicine ◽

10.18081/2333-5106/015-582-594 ◽

2015 ◽

Vol 3 (4) ◽

pp. 582-594

Author(s):

William M. Grabstald ◽

Richard H. Sarkis ◽

Chrisophos A. Jacobus ◽

Smith V. Feifer

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Cancer Staging ◽

Invasive Disease ◽

Fourth Edition ◽

Muscle Invasive Bladder Cancer ◽

Common Cancer ◽

Node Metastases ◽

Grade 3 ◽

Muscle Invasive

Bladder cancer is the second most common cancer of the genitourinary tract. Radical cystectomy is considered the gold standard of treatment for patients with localized muscle-invasive disease (MIBC), although chemoradiotherapy protocols using neoadjuvant cisplatin-based chemotherapy is used for muscle-invasive bladder cancer. We explored the toxicity and efficacy of neoadjuvant AMVAC in MIBC. A total of 177 patients with clinical tumor–node–metastases (TNM) stage T2N0M0 to T4aN0M0 bladder cancer who were candidates for radical cystectomy were eligible, tumors were staged according to the criteria in the fourth edition of the American Joint Committee on Cancer staging manual. Grade ≥ 2 toxicities were observed in 8% of patients, with grade 3 and 4 neutropenia in 7% and 5% patients, respectively; grade 3 and 4 anemia in 4% and 2% of patients, respectively; no patients died of drug toxicity; 61% of patients were accrued; 16% were down-staged to non–muscle invasive disease. Further, 31% showing pT0 at cystectomy and the median survival was 16.9 months.

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