Background: Melanoma is a cancer of the skin with potential to spread to other organs and is responsible for most deaths due to skin cancer. It is imperative to identify immune biomarkers for early melanoma diagnosis and treatment. Results: 63 immune-related genes of the total 1039 unique IRGs retrieved were associated with overall survival of melanoma. A multi-IRGs classifier constructed using eight IRGs showed a powerful predictive ability. The classifier had better predictive power compared with the current clinical data. GSEA analysis showed multiple signaling differences between high and low risk score group. Furthermore, biomarker was associated with multiple immune cells and immune infiltration in tumor microenvironment. Conclusions: The immune-related genes prognosis biomarker is an effective potential prognostic classifier in the immunotherapies and surveillance of melanoma. Methods: Melanoma samples of genes were retrieved from TCGA and GEO databases while the immunerelated genes (IRGs) were retrieved from the ImmPort database. WGCNA, Cox regression analysis and LASSO analysis were used to classify melanoma prognosis. ESTIMATE and CIBERSORT algorithms were used to explore the relationship between risk score and tumor immune microenvironment. GSEA analysis was performed to explore the biological signaling pathway.
Background Gastric cancer remains one of the major causes for tumor‐related deaths worldwide. Our study aimed to provide an understanding of primary gastric cancer and prompt its clinical diagnosis and treatment. Methods We integrated the expression profiles and overall survival information of primary gastric cancer in TCGA and GEO database and estimated the stromal score of each sample by the estimate R package. Stromal score and clinicopathologic characteristics associated with overall survival were analyzed by using Cox regression and the Kaplan‐Meier method. Gene set enrichment analysis (GSEA) and KEGG analysis were performed to explore the potential molecular mechanism in TCGA dataset. The relationship between immunotherapy‐associated markers or immune cell types and stromal score was explored by using Pearson correlation analysis. Results A total of 796 samples were collected for the analysis. Patients with stromal score‐high showed poor overall survival ( P < .01, HR: 1.407, 95% CI: 1.144‐1.731) and identified as an independent prognostic factor. KEGG analysis revealed that stromal score actively involved in diverse tumor‐associated pathways. GSEA analysis also revealed stromal score associated with diverse immune‐related biological processes. Furthermore, stromal score was related with immunotherapy‐associated markers and multiple immune cells. Conclusion Our results showed that stromal score could serve as a potential prognostic biomarker in primary gastric cancer and play an important role in the recognition, surveillance, and prognosis of gastric cancer.
Background Melanoma is a potentially fatal malignancy with poor prognosis. Several recent studies have demonstrated that combination therapy of BRAF and MEK inhibition achieved better curative effect and appeared less toxic effects. We conducted a meta‐analysis to evaluate the efficacy and safety between BRAF inhibition plus MEK inhibition combination therapy and BRAF inhibition monotherapy in melanoma patients. Methods We performed the search in PubMed, EMBASE, and the Cochrane Library from January 2010 to January 2019. Inclusion and exclusion of studies, assessment of quality, outcome measures, data extraction, and synthesis were independently accomplished by two reviewers. Revman 5.3 software was used for the meta‐analysis. Results Totally, seven randomized controlled trials involving 3146 patients met our inclusion criteria. Comparing the results of combination therapy and monotherapy, combination therapy significantly improved OS (RR = 1.13; 95% CI, 1.08, 1.19; P < 0.00001), ORR (RR = 1.36; 95% CI, 1.28, 1.45; P < 0.00001), PFS (RR = 0.57; 95% CI, 0.52, 0.63; P < 0.00001) and reduced deaths (RR = 0.78; 95% CI, 0.69, 0.88; P < 0.0001). Skin‐related adverse events such as hyperkeratosis, cutaneous squamous‐cell carcinoma were less compared with monotherapy. However, gastrointestinal events like nausea, diarrhea, and vomiting were at a higher frequency. Conclusion Doublet BRAF and MEK inhibition achieved better survival outcomes over single‐agent BRAF inhibition and occurred less skin‐related events, but gastrointestinal events were more in combination therapy.
Introduction Talaromyces marneffei ( T . marneffei ), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T . marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. Methods We retrospectively analyzed 241 patients with T . marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive ( n = 98) and HIV-negative ( n = 143) groups according to HIV status. Kaplan–Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Results With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0–68.6%) and 47.8% (95% CI 41.5–55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31–0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39–1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22–0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01–0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01–0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. Conclusions Patients with T . marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00801-5.
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