Background. To assess the prognostic value of pretreatment serum biomarkers in stage IV non-small-cell lung cancer (NSCLC) patients treated with PD-1 (programmed cell death protein 1) inhibitors and their value as a predictor of benefit. Methods. We performed a retrospective study including patients with stage IV NSCLC who were treated with anti-PD-1 drugs in first or advanced lines of therapy in the Affiliated Tumor Hospital of Nantong University. Serum biomarkers such as NLR, dNLR, LMR, PAB, ALB, and LIPI scores were calculated and analyzed in detail. Results. A total of 85 patients with stage IV NSCLC treated with PD-1 inhibitors in the first or advanced lines of therapy were included in this subject. According to the tumor response of PD-1-based treatment, ORR was 42.4% (36/85) and DCR was 68.2% (58/85). The median OS and PFS were 20.0 months and 7.0 months, respectively. The ROC curves showed that the serum biomarkers of NLR, dNLR, LDH, LMR, PAB, and ALB were significantly associated with overall survival and helped to determine the cut-off value. The multivariate Cox proportional hazard analyses for stage IV NSCLC patients treated with PD-1 inhibitors indicated that dNLR ( ) and ALB ( ) were independent prognostic indicators of PFS, while liver metastasis ( ), NLR ( ), dNLR ( ), and LMR ( ) were independent prognostic indicators of OS. Moreover, patients of the good LIPI group showed prolonged PFS and OS than those with intermediate/poor LIPI score ( and , respectively). Conclusions. Pretreatment dNLR is an independent prognostic indicator of both PFS and OS in stage IV NSCLC patients treated with PD-1 inhibitors. Pretreatment LIPI, combining and LDH>ULN, was correlated with worse outcome for stage IV NSCLC patients treated with ICI. High NLR, high dNLR, low LMR, and low ALB at baseline might be useful as an early predictive biomarker of benefit.

Objectives:This meta-analysis aims to analyze the usefulness of contrast enhanced ultrasonography (CEUS) for post-treatment responses evaluation of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) management.Methods:Literature retrieval in three databases PubMed, Embase and Cochrane Library, was conducted up to September 2015, with predefined criteria. The technical success rate, local tumor recurrence, local tumor progression were the measurement indexes. Cochran’s Q test and I2 were used for heterogeneity detection. Subgroup analyses were performed for complete ablation rate stratified by study designs, contrast agents and postoperative testing time points. Statistical analyses were conducted using Stata 12.0 software.Results:Twelve studies consisting of 772 patients were enrolled in this study. The CEUS evaluated success rate of RFA for HCCs was 91%. The proportion of ablative margin < 5 mm was 53%. The local tumor recurrence rate and local tumor progression rate were 4% and 8%, respect...

Reduced microRNA (miR)‑122 expression levels are frequently observed in hepatocellular carcinoma (HCC). The present study was conducted to investigate potential targets of miR‑122 and determine the underlying regulatory mechanisms of miR‑122 in HCC development. The public dataset GSE31731 was utilized, consisting of 8 miR‑122 knockout (KO) mice (miR‑122 KO) and 8 age‑matched wild‑type mice (WT group). Following data preprocessing, the differentially expressed genes (DEGs) were selected, followed by enrichment analysis. A protein‑protein interaction (PPI) network was established, and a module network was further extracted. Combining the DEGs with microRNA targeting databases permitted the screening of the overlapping targets of miR‑122. Furthermore, previously reported genes were screened out by literature mining. Transcription factors (TFs) of the targets were subsequently investigated. DEGs between miR‑122 KO and WT groups were selected, including 713 upregulated and 395 downregulated genes. Of these, upregulated genes were enriched in cell cycle‑associated processes [including nucleolar and spindle associated protein 1 (NUSAP1)], the cytokine‑cytokine receptor interaction pathway [including C‑X‑C motif chemokine receptor 4 (CXCR4) and C‑C motif chemokine receptor 2 (CCR2)], and the extracellular matrix‑receptor interaction pathway [including integrin subunit alpha V (ITGAV)]. In addition, multiple overlapping targets were highlighted in the PPI network, including NUSAP1, CXCR4, CCR2 and ITGAV. Notably, CXCR4 and CCR2 were linked in module C, enriched in the cytokine‑cytokine receptor interaction pathway. Furthermore, upregulated sex determining region Y‑box 4 (SOX4) was identified as a TF. The results of the present study may provide a theoretical basis for further studies on the mechanisms of miR‑122 in the development of HCC.

Background: Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear. Methods: The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M survival analysis was also conducted to evaluate the impact of TTK on survival outcomes. Protein‒protein interaction (PPI) networks associated with TTK were explored using the STRING database. Functional enrichment analysis was performed to elucidate the biological functions of TTK. TTK mRNA expression and immune infiltration correlations were examined using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction Database (TISIDB). Results: TTK expression was significantly greater in EC tissues than in adjacent normal tissues. Higher TTK mRNA expression was associated with tumor metastasis and advanced TNM stage. The protein and mRNA expression of TTK was significantly greater in tumor cell lines than in normal endometrial cell lines. ROC curve analysis revealed high accuracy (94.862%), sensitivity (95.652%), and specificity (94.894%) of TTK in differentiating EC from normal tissues. K-M survival analysis demonstrated that patients with high TTK expression had worse overall survival (OS) and disease-free survival (DFS) rates. Correlation analysis revealed that TTK mRNA expression was correlated with B cells and neutrophils. Conclusion: TTK upregulation is significantly associated with poor survival outcomes and immune infiltration in patients with EC. TTK can serve as a potential biomarker for poor prognosis and a promising immunotherapy target in EC. Further investigation of the role of TTK in EC may provide valuable insights for therapeutic interventions and personalized treatment strategies.

Tumor microenvironment (TME) plays a crucial role in sustaining cancer stem cells (CSCs). 4-hydroxynonenal (4-HNE) is abundantly present in the TME of colorectal cancer (CRC). However, the contribution of 4-HNE to CSCs and cancer progression remains unclear. This study aimed to investigate the impact of 4-HNE on the regulation of CSC fate and tumor progression. Human CRC cells were exposed to 4-HNE, and CSC signaling was analyzed using quantitative real-time PCR, immunofluorescent staining, fluorescence-activated cell sorting, and bioinformatic analysis. Tumor-promoting role of 4-HNE was confirmed using a xenograft model. Exposure of CRC cells to 4-HNE activated non-canonical Hedgehog (HH) signaling and homologous recombination repair (HRR) pathways in LGR5+ CSCs. Furthermore, blocking HH signaling led to a significant increase in the expression of γH2AX, indicating that 4-HNE induces double-stranded DNA breaks (DSBs) and simultaneously activates HH signaling to protect CSCs from 4-HNE-induced damage via the HRR pathway. Additionally, 4-HNE treatment increased the population of LGR5+ CSCs and promoted asymmetric division in these cells, leading to enhanced self-renewal and differentiation. Notably, 4-HNE also promoted xenograft tumor growth and activated CSC signaling in vivo. These findings demonstrate that 4-HNE, as a signaling inducer in the TME, activates the non-canonical HH pathway to shield CSCs from oxidative damage, enhances the proliferation and asymmetric division of LGR5+ CSCs, and thereby facilitates tumor growth. These novel insights shed light on the regulation of CSC fate within the oxidative TME, offering potential implications for understanding and targeting CSCs for CRC therapy.

Background. The leading cause of cancer‐related fatalities globally is lung cancer; lung adenocarcinoma (LUAD) is the most common histological type in it. The spliceosome plays an important role in a majority of malignancies. However, it is yet unclear how spliceosome‐related genes affect patients with LUAD in terms of treatment course and prognosis. Methods. Spliceosome‐related genes were assessed from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to obtain clinical information and gene expression in patients with LUAD. A spliceosome‐related gene signature and prognostic model were constructed by using the least absolute shrinkage and selection operator (LASSO), time‐dependent receiver operating characteristic (ROC), and nomogram. Immune infiltrate levels, mutation analysis, and pathway enrichment were predicted potential mechanisms of the signature by using single‐sample gene set enrichment analysis (ssGSEA), Gene Set Cancer Analysis (GSCA) database, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) database. Then, a protein–protein interaction (PPI) network and transcription factor‐ (TF‐) hub gene and drug mining network were also established by Cytoscape software. Results. Firstly, we constructed a prognostic model for 11 spliceosome signature genes. Based on the prognostic risk score, we stratified patients with LUAD into high‐ and low‐risk groups. The high‐ and low‐risk groups were closely related to the OS, tumor immune infiltration level, immune checkpoint molecules, and tumor mutation burden (TMB) of LUAD patients. Based on PPI networks, we also predict relevant TF genes that may regulate signature prognostic genes. Finally, drugs including oxaliplatin, arsenic trioxide, cisplatin, and sunitinib were excavated for the treatment of the 11 spliceosome signature genes in LUAD patients. Conclusion. In conclusion, this study is the first to explore the importance of spliceosome‐related genes in the prognosis and treatment of LUAD. Through our study, we have innovatively provided potential prognosis genes and new therapeutic drug targets for the treatment of LUAD patients.