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.

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy.

Background: Uveal melanoma (UVM) is a primary intraocular malignancy that poses a significant threat to patients' visual function and life. The basement membrane (BM) is critical for establishing and maintaining cell polarity, adult function, embryonic and organ morphogenesis, and many other biological processes. Some basement membrane protein genes have been proven to be prognostic biomarkers for various cancers. This research aimed to develop a novel risk assessment system based on BMRGs that would serve as a theoretical foundation for tailored and accurate treatment. Methods: We used gene expression profiles and clinical data from the TCGA-UVM cohort of 80 UVM patients as a training set. 56 UVM patients from the combined cohort of GSE84976 and GSE22138 were employed as an external validation dataset. Prognostic characteristics of basement membrane protein-related genes (BMRGs) were characterized by Lasso, stepwise multifactorial Cox. Multivariate analysis revealed BMRGs to be independent predictors of UVM. The TISCH database probes the crosstalk of BMEGs in the tumor microenvironment at the single-cell level. Finally, we investigated the function of ITGA5 in UVM using multiple experimental techniques, including CCK8, transwell, wound healing assay, and colony formation assay. Results: There are three genes in the prognostic risk model (ADAMTS10, ADAMTS14, and ITGA5). After validation, we determined that the model is quite reliable and accurately forecasts the prognosis of UVM patients. Immunotherapy is more likely to be beneficial for UVM patients in the high-risk group, whereas the survival advantage may be greater for UVM patients in the low-risk group. Knockdown of ITGA5 expression was shown to inhibit the proliferation, migration, and invasive ability of UVM cells in vitro experiments. Conclusion: The 3-BMRGs feature model we constructed has excellent predictive performance which plays a key role in the prognosis, informing the individualized treatment of UVM patients. It also provides a new perspective for assessing pre-immune efficacy.

Identification and validation of neurotrophic factor-related genes signature in HNSCC to predict survival and immune landscapes.

Background: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer worldwide. Its highly aggressive and heterogeneous nature and complex tumor microenvironment result in variable prognosis and immunotherapeutic outcomes for patients with HNSCC. Neurotrophic factor-related genes (NFRGs) play an essential role in the development of malignancies but have rarely been studied in HNSCC. The aim of this study was to develop a reliable prognostic model based on NFRGs for assessing the prognosis and immunotherapy of HNSCC patients and to provide guidance for clinical diagnosis and treatment. Methods: Based on the TCGA-HNSC cohort in the Cancer Genome Atlas (TCGA) database, expression profiles of NFRGs were obtained from 502 HNSCC samples and 44 normal samples, and the expression and prognosis of 2601 NFRGs were analyzed. TGCA-HNSC samples were randomly divided into training and test sets (7:3). GEO database of 97 tumor samples was used as the external validation set. One-way Cox regression analysis and Lasso Cox regression analysis were used to screen for differentially expressed genes significantly associated with prognosis. Based on 18 NFRGs, lasso and multivariate Cox proportional risk regression were used to construct a prognostic risk scoring system. ssGSEA was applied to analyze the immune status of patients in high- and low-risk groups. Results: The 18 NFRGs were considered to be closely associated with HNSCC prognosis and were good predictors of HNSCC. The multifactorial analysis found that the NFRGs signature was an independent prognostic factor for HNSCC, and patients in the low-risk group had higher overall survival (OS) than those in the high-risk group. The nomogram prediction map constructed from clinical characteristics and risk scores had good prognostic power. Patients in the low-risk group had higher levels of immune infiltration and expression of immune checkpoints and were more likely to benefit from immunotherapy. Conclusion: The NFRGs risk score model can well predict the prognosis of HNSCC patients. A nomogram based on this model can help clinicians classify HNSCC patients prognostically and identify specific subgroups of patients who may have better outcomes with immunotherapy and chemotherapy, and carry out personalized treatment for HNSCC patients.

SLC22A8: An indicator for tumor immune microenvironment and prognosis of ccRCC from a comprehensive analysis of bioinformatics.

Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies worldwide. SLC22A8 plays a key role in renal excretion of organic anions. However, its role in ccRCC remains unclear; therefore, this study aimed to elucidate the relationship between SLC22A8 and ccRCC. The The Cancer Genome Atlas-kidney renal clear cell carcinoma cohort was included in this study. The Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between SLC22A8 expression and clinicopathological characteristics. Multifactorial analysis and Kaplan-Meier survival curves were adopted for correlation between SLC22A8 expression and clinicopathological parameters and overall survival. Utilizing the UALCAN database, the correlation of the expression levels of SLC22A8 DNA methylation in ccRCC was explored. Immunological characterization of SLC22A8 regarding the ccRCC tumor microenvironment was carried out by the single sample Gene Set Enrichment Analysis algorithm and the CIBERSORT algorithm. With the CellMiner database, the analysis of the association between SLC22A8 gene expression and drug sensitivity was further performed. Eventually, gene ontology and Kyoto Encyclopedia of Gene and Genome enrichment analyses were applied to identify the functional and signaling pathways involved in SLC22A8. SLC22A8 expression is associated with age, grade, stage, and tumor status. SLC22A8 protein expression levels, phosphorylated protein levels, and DNA methylation expression levels were lower in ccRCC tissues than in normal tissues, and low methylation levels predicted poor overall survival. Comprehensive analysis of tumor immune infiltration and the tumor microenvironment indicated a higher level of overall immunity in the SLC22A8 low expression group. Gene Enrichment Analysis results showed that low expression of SLC22A8 was associated with immune pathways, such as phagocytosis recognition and humoral immune response. SLC22A8 expression was significantly correlated with survival and immune infiltration in ccRCC and can be used as a prognostic biomarker for ccRCC.

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.

Physiological response of Conyza Canadensis to cadmium stress monitored by Fourier transform infrared spectroscopy and cadmium accumulation.

The cadmium(Cd) pollution of soil causes serious environmental problems. Cd is a high toxic and high water soluble element without biological function, and it is easily taken in by plants owing to its high bioavailability. Thus it easily entered the food chain and threaten people's health. Here，different concentrations of Cd solutions were used to study the physiological response and Cd accumulation characteristics of Conyza Canadensis (L.) Cronq. The physiological response was characterized by Fourier Transform Infrared (FTIR) spectroscopy, and Cd accumulation in plant and distribution were tested by Atomic absorption spectroscopy (AAS) under different concentrations Cd stress. When Cd concentrations toxicity <3 mg·L-1, the C. Canadensis (L.) Cronq. could grow normally without any symptoms, and the Cd concentrations increased to 7 mg·L-1, the C. Canadensis (L.) Cronq. had a little lower biomass, but there was no significant difference in the biomass among treatment concentrations. The peak shape of each component remained unchanged before and after Cd treatment. Only the absorption peak of some functional groups involved in Cd adsorption shifted with different degrees, such as hydroxy groups (3417-3429 cm-1), carboxyl groups (1380-1386 cm-1), and acid amide groups (1631-1637 cm -1). The characteristic peak absorption intensity of root, stem and leaf was different with the increase of heavy metal concentration. The absorbance of the roots with high Cd concentration was higher than that with medium-low Cd concentration. This shows that high concentration of Cd could induce C. Canadensis (L.) Cronq. seedlings to produce a large number of protein, amino acid and other substances, and through osmotic regulation to enhance stress resistance, provide nitrogen source, reduce heavy metal toxicity, and stabilize the internal environment. After Cd treatment, the characteristic peaks of stem and leaf were higher than or close to the control. This is due to the high tolerance of C. Canadensis (L.) Cronq. seedlings to heavy metals. The Cd accumulation in the shoots (stems and leaves) of C. Canadensis (L.) Cronq. was obviously lower than that in roots and the Cd content in the shoots usually increased with increasing Cd concentration. The maximum accumulation of Cd in shoots was 1898.07 mg·kg-1 after 11 days grown in the water spiked with 7 mg·L-1 Cd concentration. The study suggests that C. Canadensis (L.) Cronq. has some remediation effect and endurance ability against heavy metal polluted contaminated soil and has potential utilization value in the technical field of phytoremediation of Cd polluted soil.