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Purpose To investigate the accuracy and the discriminatory performance in the prognostic prediction in breast cancer (BC) patients with ipsilateral supraclavicular lymph node (ISLN) metastasis using the between the American Joint Committee on Cancer (AJCC) 7th and 8th edition staging system. Methods Female patients diagnosed as BC were retrieved from the Surveillance, Epidemiology, and End Results database between 2010 and 2014. Chi-squared test, Kaplan-Meier method, Cox proportional hazard analysis, and the receiver operating characteristics were used to conduct statistical analysis. Results We included 1097 BC patients with ISLN metastasis (N3c disease), including 29.4% (n=322) and 70.6% (n=775) of patients with non-metastatic and metastatic stage at diagnosis, respectively. In non-metastatic stage patients, 64.9% of the patients categorized as having stage IIIC disease in the 7th edition AJCC staging system were downstaged to stage IIIA or IIIB according to the 8th AJCC staging criteria. The AJCC 8th edition staging system had better discriminatory prognostic value than the 7th AJCC staging (area under the curve 0.586 vs. 0.577, P=0.0006), with a 5-year breast cancer-specific survival (BCSS) rate of 71.3%, 62.2%, 45.2% and 39.1% in stage IIIA, IIIB, IIIC, and IV cohorts, respectively (P less then 0.0001). The multivariate prognostic analysis revealed that the AJCC 8th edition staging system was an independent prognostic factor for BCSS, while no statistical difference in BCSS was found between the 8th AJCC stage IIIC and IV patients (P=0.188). Conclusion The AJCC 8th edition pathological prognostic staging showed a better discriminatory prognostic value in ISLN-metastasized breast cancer patients. An additional clarification strategy in stage IIIC disease based on the 8th AJCC staging should be developed to differentiate patients who are curable with multimodality therapy and patients who have less benefit from curative treatment.The purpose of this study was to investigate the genetic variation, gene expression differences, and clinical significance of SUMOylation regulators in pan-cancers. Based on previous studies, we gained a better understanding of the biological process of SUMOylation and the status of current research. In the present study, we employed a wide range of bioinformatics methods. We used genetic variation and mRNA expression data in the Cancer Genome Atlas (TCGA) to construct a panoramic view of the single nucleotide variants, copy number variants, and gene expression changes in SUMOylation regulators in various tumors. Subsequently, we used the String website and the Cytoscape tool to construct the PPI network between these regulators. We used the GSCALite website to determine the relationship between these regulators and cancer pathways and drug sensitivity. We constructed images of co-expression between these regulators using the R programming language. Using clinical data from TCGA, we performed hazard ratio analysis for these regulators in pan-cancer. Most importantly, we used these regulators to successfully establish risk signatures related to patient prognosis in multiple tumors. Finally, in KIRC, we conducted gene-set enrichment analysis (GSEA) of the five molecules in its risk signatures. We found that these five molecules are involved in multiple cancer pathways. In short, we have comprehensively interpreted the detailed biological process of SUMOylation at the genetic level for the first time, successfully constructed multiple risk signatures, and conducted GSEA in KIRC. SB939 manufacturer We believe that these findings provide credible and valuable information that is relevant for future clinical diagnoses and scientific research.Serum cancer biomarker has been proven to be very valuable in cancer diagnosis, disease monitoring and prognosis assessment, despite there is still a lack of serum biomarker for penile cancer (PC). Our initial analysis on public GEO dataset identified CCL20 as a top C-C motif ligand (CCL) gene enriched in PC. The patients with PC exhibited markedly higher preoperative serum CCL20 level than healthy control. The area under the curve (AUC) was 0.855 with the sensitivity of 72.4%, and specificity of 93.5% to distinguish PC. Preoperative serum CCL20 level was significantly associated with clinicopathological characteristics including T stage (P=0.005), nodal status (P=0.008), and pelvic lymph node metastasis (P=0.007). PC Patients with high serum CCL20 level had shorter disease-free survival compared to those with low level (P less then 0.001). Cox regression analysis showed that serum CCL20 level could serve as an independent prognostic factor for disease-free survival with a HR of 3.980 (95% CI 1.209-13.098, P=0.023). Furthermore, CCL20 expression was observed in PC tissues and cell lines. Knockdown of CCL20 expression markedly suppressed malignant phenotypes (cell proliferation, clonogenesis, apoptosis escape, migration and invasion), attenuated STAT3 and AKT signaling and reduced MMP2/9 secretion in PC cell lines. Consistently, CCL20 and its receptor CCR6 exhibited correlated expression pattern in PC tissues. In conclusion, serum CCL20 level might serve as a potential diagnostic and prognostic cancer biomarker for PC. CCL20 might activate multiple downstream oncogenic signaling pathways (STAT3, AKT, MMP2/9) to promote malignant progression of PC, which may warrant further investigation in the future.Purpose Ubiquitin specific peptidase 5 (USP5) has been reported to promote the progression of several malignant tumors. It may affect cancer development via modulating cell cycle and colony formation. In pancreatic cancer, the biological function of USP5, especially in migration and invasion remains unclear. Methods USP5 protein expression levels in primary pancreatic cancer and lymph node metastasis tissues were detected using immunohistochemistry (IHC). χ2 test, Kaplan-Meier analysis, univariate and multivariate analyses were used to evaluate the relationship between USP5 expression and clinicopathological feature. RT-qPCR were carried out to quantitate the mRNA expression levels of USP5 in pancreatic cancer cell lines. CCK8 and Colony formation assay were performed to prove how USP5 works in proliferation. Evaluation of tumor metastasis was made by Transwell and wound healing assay. EMT and STAT3 signaling related markers were detected by western blot. Results (1) USP5 protein expression levels were related to tumor differentiation, CEA and CA19-9 level.

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