XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis.

X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, a comprehensive pan-cancer analysis investigating the prognostic value, immunological functions, and epigenetic associations of XRCC1 remains lacking. To address this knowledge gap, we conducted a systematic investigation employing bioinformatics techniques across 33 cancer types. Our analysis encompassed XRCC1 expression levels, prognostic and diagnostic implications, epigenetic profiles, immune and molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), immune checkpoints, and immune infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, and cBioPortal databases. Notably, XRCC1 displayed both positive and negative correlations with prognosis across different tumors. Epigenetic analysis revealed associations between XRCC1 expression and DNA methylation patterns in 10 cancer types, as well as enhanced phosphorylation. Furthermore, XRCC1 expression demonstrated associations with TMB and MSI in the majority of tumors. Interestingly, XRCC1 gene expression exhibited a negative correlation with immune cell infiltration levels, except for a positive correlation with M1 and M2 macrophages and monocytes in most cancers. Additionally, we observed significant correlations between XRCC1 and immune checkpoint gene expression levels. Lastly, our findings implicated XRCC1 in DNA replication and repair processes, shedding light on the precise mechanisms underlying its oncogenic effects. Overall, our study highlights the potential of XRCC1 as a prognostic and immunological pan-cancer biomarker, thereby offering a novel target for tumor immunotherapy.

Efficacy and Pharmacological Mechanism of Poria cocos-Based Formulas Combined With Chemotherapy for Ovarian Cancer: A Integrated Systems Pharmacology Study.

Previous studies have shown that Poria cocos-based formulas combined with chemotherapy can improve the quality of life of ovarian cancer patients. However, the results are still controversial. We systematically searched the literature from eight databases to evaluate the efficacy and safety of Poria cocos-based formulas in combination with paclitaxel-carboplatin in treating ovarian cancer (OC). Subsequently, network pharmacology, molecular docking and cell experiments were performed to further verify the underlying molecular mechanism. Thirteen randomized controlled trials, including 922 patients with OC, were enrolled in the study. The results indicated that Poria cocos-based compounds combined with paclitaxel-carboplatin significantly improved patients' tumor response rate, traditional Chinese medicine syndrome score, Karnofsky Performance Scale, physical and social function, and reduced side effects of chemotherapy compared to the paclitaxel-carboplatin alone. According to the network pharmacological analysis, tumulosic acid were the most bioactive compounds of Poria cocos. BCL2L1 is highly expressed in OC and is associated with a worse prognosis which could become potential drug target. Functional enrichment analysis suggested that the anti-OC effect of Poria cocos may be related to PI3K-Akt signaling pathway. The molecular docking results indicated that tumulosic acid might inhibit OC by regulating BCL2L1. Vitro experiment confirmed tumulosic acid that induced cell apoptosis by modulating PI3K/AKT signaling and BCL2L1. Our study may provide a clinical basis and theoretical rationale for combining Poria cocos-based formulas with chemotherapy for OC. In addition, the integrated pharmacological strategy proposed in our study provides an excellent example for exploring the mechanism of complex formulas.

Mechanism Prediction of Astragalus membranaceus against Cisplatin-Induced Kidney Damage by Network Pharmacology and Molecular Docking.

BACKGROUND: Cisplatin is a frequently used and effective chemotherapy drug in clinical practice, but severe side effects limit its use, among which nephrotoxicity is considered the most serious and prolonged damage to the body. Astragalus membranaceus (AM) is a well-known herbal medicine, and modern pharmacological studies have confirmed its antioxidant, immunomodulatory, and antiapoptotic effects. Clinical studies have shown that AM and its active components can attenuate cisplatin-induced kidney damage, but the molecular mechanism has not been fully expounded. MATERIALS AND METHODS: First, the components and targets information of AM were collected from the TCMSP, and the relevant targets of cisplatin-induced kidney damage were accessed from the GeneCards and OMIM databases. Then, the core targets were selected by the Venn diagram and network topology analysis, which was followed by GO and KEGG pathway enrichment analysis. Finally, we construct a component-target-pathway network. Furthermore, molecular docking was carried out to identify the binding activity between active components and key targets. RESULTS: A total of 20 active components and 200 targets of AM and 646 targets related to cisplatin-induced kidney damage were obtained. 91 intersection targets were found between AM and cisplatin-induced kidney damage. Then, 16 core targets were identified, such as MAPK1, TNF-α, and p53. Furthermore, GO and KEGG pathway enrichment analysis suggested that MAPK, Toll-like receptor, and PI3K-Akt signaling pathways may be of significance in the treatment of cisplatin-induced kidney damage by AM. Molecular docking indicated that quercetin and kaempferol had high binding affinities with many core targets. CONCLUSION: In summary, the active components, key targets, and signaling pathways of AM in the treatment of cisplatin-induced kidney damage were predicted in this study, which contributed to the development and application of AM.