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Objectives: Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate, regulates various biological processes related to tumor progression. We explore the prognostic value of HPSE and its relationship with immunotherapy response in patients with breast cancer, to improve the effectiveness of immunotherapy and increase the survival outcomes. Methods: In the study, we explored the prognostic value of HPSE through the The Cancer Genome Atlas (TCGA) database. By using the single-sample gene set enrichment analysis (ssGSEA) method, we measured the infiltration levels of 24 immune cell types in the tumor microenvironment. Cancer Therapeutics Response Portal (CTRP) and PRISM datasets provide the area under the dose-response curve (AUC) to measure drug sensitivity. Using nomograms, we predicted overall survival ability. In vivo studies, we investigated the relationship between HPSE and immune checkpoint proteins and pro-inflammatory cytokines by immunohistochemistry of Triple-Negative Breast Cancer tumors in mice. Results: Our model demonstrated that the integrating of HPSE with the clinical stage effectively predicts patients' survival time, highlighting high HPSE expression as a prognostic risk factor for breast cancer. Then the Receiver Operating Characteristic (ROC) curve [AUC of 1 year = 0.747, AUC of 3 years = 0.731] and Decision Curve Analysis (DCA) curve illustrated the satisfactory discriminative capacity of our model, emphasizing its valuable clinical applicability. Immune-related results showed that HPSE correlates strongly with immune infiltrating cells, immune-related genes, and the anti-cancer immunity cycle. In vivo studies have demonstrated that HPSE in breast cancer is associated with increased expression of immune checkpoint proteins CD274 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and is positively correlated with the pro-inflammatory cytokine TNF-α. Meanwhile, we analyzed the 11 types of drugs that are sensitive to the HPSE gene. Conclusion: Our results show that HPSE can serve as an effective biomarker to predict the prognosis of breast cancer patients and reflect the impact of immunotherapy. [ABSTRACT FROM AUTHOR]

A potential relationship between poor prognosis and thrombocytosis has been suggested by previous studies in lung cancer, but the conclusions continued to be controversial. Here, we performed a meta-analysis to explore the prognostic impact of thrombocytosis in lung cancer. The Cochrane Library, EMBASE and PubMed databases were comprehensively and systematically retrieved from establishment to May 5, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate overall effects. Heterogeneity was assessed using I2 statistics and Cochran's Q test. Sensitivity and subgroup analyses were performed to analyze the sources of heterogeneity. Publication bias was examined using the Egger's test and pooled HR was regulated using the trim-and-fill approach when publication bias was observed. A total of 37 studies including 14,833 patients were enrolled in the meta-analysis. Thrombocytosis was significantly correlated to poor overall survival (HR 1.033; 95% CI 1.017–1.050), disease-free survival (HR 1.568; 95% CI 1.276–1.928), and progression-free survival (HR 1.653; 95% CI 1.069–2.556). Although publication bias was identified, rectification for this bias using the trim-and-fill approach did not change the combined HR substantially. In conclusion, this meta-analysis result suggested that thrombocytosis is a predictor of poor prognosis in lung cancer. [ABSTRACT FROM AUTHOR]

For the treatment of hepatocellular carcinoma (HCC), compound Kushen injection (CKi) is commonly used in combination with transarterial chemoembolization (TACE). Our objective was to evaluate the reporting quality, methodological quality, risk of bias, and certainty of evidence for CKi combined with TACE for the treatment of patients with HCC by conducting systematic reviews (SRs). The purpose of this study was to improve the clinical application of CKis, strengthen clinical decision-making regarding CKis, and inform future research. We used eight databases to systematically search SRs of CKi combined with TACE for HCC through February 21, 2023. The quality of reporting of SRs was evaluated using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, methodological quality using A MeaSurement Tool to Assess systematic Reviews 2, risk of bias using the Risk of Bias in Systematic Review, and certainty of evidence using the Grading of Recommendations Assessment. Finally, the assessment results were visualized by the evidence mapping method. This overview has been registered on PROSPERO with the registration title "Compound Kushen injection for hepatocellular carcinoma: An overview of systematic reviews" and registration number CRD42022369120. A total of 12 SRs meeting the inclusion criteria were included. In terms of reporting quality, 42% of SRs reported relatively complete reports and 58% had certain deficiencies. The methodological quality of all SRs was " critically low". The risk of bias was evaluated as low in 33% of SRs and high in 67% of SRs. The results of the evidence synthesis showed that, in the "moderate" level of evidence, CKi combined with TACE resulted in a 12.7%–21.5% benefit for one-year survival rate, 11.7%–17.2% benefit for objective response rate (ORR), 20.5%–27.1% benefit for quality of life, 22.2% benefit for nausea and vomiting, and 24.7%–27.4% benefit for leukopenia in HCC patients. In conclusion, CKi combined with TACE improved survival, ORR and quality of life in patients with HCC, and reduced adverse events. The results should be interpreted with caution due to the low methodological quality of the included SRs. The clinical efficacy of CKis must be confirmed in a large number of randomized controlled trials. [Display omitted] • The "Moderate" evidence for CKi in combination with TACE for HCC was summarized. • The methodological quality, reporting quality and risk of bias of SRs are summarized. • Answers what benefits CKi combined with TACE can bring to HCC patients. • Explains how much benefit CKi combined with TACE can bring to HCC patients. [ABSTRACT FROM AUTHOR]