Zimberelimab combined with systemic therapy extended tumor control in post-radiotherapy cervical cancer with brain metastases: A case report.

Out of the total cases of cervical cancer, brain metastases (BMs) are relatively rare, with an estimated incidence rate of 0.63% (range: 0.1%-2.2%). Additionally, BMs prognosis remains poor, and the average patient survival time following a BM diagnosis is 3 to 5 months. Few studies have addressed the effect of programmed cell death-1 inhibitors against BMs in cervical cancer, although they are an established option for recurrent/metastatic disease. Hence, we report a case involving a 54-year-old post-surgery patient with cervical cancer with a body mass index of 19.5 kg/m2 and Eastern Collaborative Oncology Group (ECOG) performance status of 3; the disease recurred with BMs 1 year later. Intensity-modulated radiation therapy concurrent with temozolomide and bevacizumab was initiated, following which zimberelimab immunotherapy combined with anlotinib was administered to extend tumor control. The patient had a progression-free survival duration of 10 months, the tumor response was assessed as a partial response based on the evaluation criteria for solid tumors (RECIST1.1), and the ECOG status improved to 1 after therapy. These findings suggest that immunotherapy-based combination therapy following radiotherapy may be a good choice for patients with cervical cancer and BMs.

Implications of inflammatory cell death-related IFNG and co-expressed RNAs (AC006369.1 and CCR7) in breast carcinoma prognosis, and anti-tumor immunity.

Objective: Interferon-γ (IFN-γ) encoded by IFNG gene is a pleiotropic molecule linked with inflammatory cell death mechanisms. This work aimed to determine and characterize IFNG and co-expressed genes, and to define their implications in breast carcinoma (BRCA). Methods: Transcriptome profiles of BRCA were retrospectively acquired from public datasets. Combination of differential expression analysis with WGCNA was conducted for selecting IFNG-co-expressed genes. A prognostic signature was generated through Cox regression approaches. The tumor microenvironment populations were inferred utilizing CIBERSORT. Epigenetic and epitranscriptomic mechanisms were also probed. Results: IFNG was overexpressed in BRCA, and connected with prolonged overall survival and recurrence-free survival. Two IFNG-co-expressed RNAs (AC006369.1, and CCR7) constituted a prognostic model that acted as an independent risk factor. The nomogram composed of the model, TNM, stage, and new event owned the satisfying efficacy in BRCA prognostication. IFNG, AC006369.1, and CCR7 were closely linked with the tumor microenvironment components (e.g., macrophages, CD4/CD8 T cells, NK cells), and immune checkpoints (notably PD1/PD-L1). Somatic mutation frequencies were 6%, and 3% for CCR7, and IFNG, and high amplification potentially resulted in their overexpression in BRCA. Hypomethylated cg05224770 and cg07388018 were connected with IFNG and CCR7 upregulation, respectively. Additionally, transcription factors, RNA-binding proteins, and non-coding RNAs possibly regulated IFNG and co-expressed genes at the transcriptional and post-transcriptional levels. Conclusion: Collectively, our work identifies IFNG and co-expressed genes as prognostic markers for BRCA, and as possible therapeutic targets for improving the efficacy of immunotherapy.

Seven Hub Genes Predict the Prognosis of Hepatocellular Carcinoma and the Corresponding Competitive Endogenous RNA Network.

Purpose: This study was aimed at identifying hub genes and ceRNA regulatory networks linked to prognosis in hepatocellular carcinoma (HCC) and to identify possible therapeutic targets. Methods: Differential expression analyses were performed to detect the differentially expressed genes (DEGs) in the four datasets (GSE76427, GSE6764, GSE62232, and TCGA). The intersected DEmRNAs were identified to explore biological significance by enrichment analysis. We built a competitive endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA. The mRNAs of the ceRNA network were used to perform Cox and Kaplan-Meier analyses to obtain prognosis-related genes, followed by the selection of genes with an area under the curve >0.8 to generate the random survival forest model and obtain feature genes. Furthermore, the feature genes were subjected to least absolute shrinkage and selection operator (LASSO) and univariate Cox analyses were used to identify the hub genes. Finally, the infiltration status of immune cells in the HCC samples was determined. Results: A total of 1923 intersected DEmRNAs were identified in four datasets and involved in cell cycle and carbon metabolism. ceRNA network was created using 10 lncRNAs, 67 miRNAs, and 1,923 mRNAs. LASSO regression model was performed to identify seven hub genes, SOCS2, MYOM2, FTCD, ADAMTSL2, TMEM106C, LARS, and KPNA2. Among them, TMEM106C, LARS, and KPNA2 had a poor prognosis. KPNA2 was considered a key gene base on LASSO and Cox analyses and involved in the ceRNA network. T helper 2 cells and T helper cells showed a higher degree of infiltration in HCC. Conclusion: The findings revealed seven hub genes implicated in HCC prognosis and immune infiltration. A corresponding ceRNA network may help reveal their potential regulatory mechanism.

Prognostic Value of the Glasgow Prognostic Score on Overall Survival in patients with Advanced Non-Small Cell Lung Cancer.

Background: Findings from previous studies regarding the association between the Glasgow Prognostic Score (GPS) and overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) were limited. This study aimed to investigate the prognostic value of GPS in patients with advanced NSCLC after adjusting for potential confounding factors. Methods: A retrospective cohort study was conducted in 494 patients with advanced NSCLC between 2009 and 2019. Clinicopathological characteristics (including GPS) were analyzed to determine predictors of OS using univariate and multivariate Cox proportional hazards models. Survival curves were estimated using the Kaplan-Meier method. Results: Of the enrolled patients with advanced NSCLC, 66.46% were men and 53.85% were aged <60 years. The percentages of GPS scores of 0, 1, and 2 were 36.44%, 36.03%, and 27.53%, respectively. The median OS of the GPS 0, 1, and 2 groups were 23.27, 14.37, and 10.27 months, respectively (log-rank P <0.0001). A higher GPS was independently associated with an increased risk of death (P for trend = 0.0004) after full adjustment for potential confounders. The risk of death increased by 77% in the GPS 1 group (hazard ratio [HR]=1.77, 95% confidence interval [CI]=1.22-2.57, P=0.0027) and 109% in the GPS 2 group (HR=2.09, 95%CI=1.36-3.22, P=0.0008) compared with the GPS 0 group after adjustment. We did not find significant heterogeneity among the analyzed subgroups apart from sex (P interaction=0.017). Conclusion: High pretreatment GPS is independently associated with worse OS in patients with advanced NSCLC. GPS should be considered in patient counseling and decision-making and needs to be further validated by large-cohort and prospective studies.