Immune checkpoint inhibitors have revolutionized the treatment strategy of esophageal squamous cell carcinoma (ESCC). The value of ctDNA dynamic changes in ESCC patients treated with immunochemotherapy was not clear.

Colorectal cancer liver metastasis generally refers to the process where colorectal cancer cells enter the liver through the bloodstream and form new tumors within the liver. The roles of complexin 2 (CPLX2) and synaptosome-associated protein 25 (SNAP25) in the recovery from colorectal cancer liver metastasis are not yet clear. Data sets GSE147602 and GSE144259 for colorectal cancer liver metastasis were downloaded from the gene expression omnibus database generated from GPL21047 and GPL11154. Batch normalization, differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis, construction and analysis of the protein-protein interaction network, functional enrichment analysis, and Gene Set Enrichment Analysis were conducted. Heatmaps of gene expression were plotted. Immune infiltration analysis and Comparative Toxicogenomics Database analysis were performed. TargetScan was used to screen for miRNAs regulating central DEGs. Through experimental verification, a total of 1215 DEGs were identified. According to gene ontology analysis, they were mainly enriched in cell signaling, G-protein-coupled receptor signaling pathway, signal transduction receptor binding, and cytokine binding. Kyoto Encyclopedia of Genes and Genomes analysis results showed that the target cells were mainly enriched in cholesterol metabolism olfactory transduction. In the enrichment projects of metascape, gene ontology enrichment items included regulation of circulation, muscle structure development, vascular process in the circulatory system, and extracellular matrix organization. The soft-thresholding power for weighted gene co-expression network analysis was set to 4. Four core genes were obtained by intersecting the central genes identified by 5 different algorithms, as shown in a Venn diagram. The heatmap of gene expression showed that the core genes (CPLX2, SNAP25, and Bassoon) were underexpressed in primary colorectal cancer and overexpressed in colorectal cancer liver metastasis. Comparative Toxicogenomics Database analysis showed that 3 genes (CPLX2, SNAP25, and Bassoon) were related to abdominal pain, jaundice, chemical and drug-induced liver injury, and necrosis. The related miRNAs for the CPLX2 gene were hsa-miR-1-3p, hsa-miR-206, hsa-miR-613; for the SNAP25 gene were hsa-miR-181d-5p, hsa-miR-181b-5p, hsa-miR-181c-5p. The results confirmed that CPLX2 and SNAP25 positively regulated the phosphatidylinositol 3 kinase-AKT signaling pathway and promoted the progression of liver metastasis of colorectal cancer. CPLX2 and SNAP25 genes are overexpressed in colorectal cancer liver metastasis and may serve as important molecular targets.

The clinical management of patients with both coronavirus disease 2019 (COVID-19) and breast cancer remains a complex and unresolved issue that despite extensive discussion has not reached a consensus. In contemporary literature, the association between COVID-19 and HER2-positive breast cancer has received minimal attention. Genetic instruments for severe acute respiratory syndrome coronavirus 2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critically ill COVID-19 (N = 1,086,211) were obtained from the COVID-19 Host Genetics Initiative genome-wide association study (GWAS) meta-analysis. A total of 103,530 HER2-positive breast cancer cases from GWAS were enrolled in our study. The summary GWAS statistics of 731 immune cells (N = 3757) were obtained from the MRCEU open database. Causal associations were evaluated by applying Mendelian randomization (MR) including inverse variance weighting, MR-Egger regression, and weighted-median analysis. Sensitivity analyses were employed, including Cochran Q test, MR-Egger intercept test, MR Pleiotropy Residual Sum and Outlier, and leave-one-out analysis, to examine the robustness of these findings. Genetic liability to critically ill COVID-19 was significantly causally associated with the increased risk of HER2-positive breast cancer (odds ratios = 1.086, 95% confidence intervals = 1.015-1.162, P = .016). No causal associations between severe acute respiratory syndrome coronavirus 2 infection or hospitalized COVID-19 and HER2-positive breast cancer were observed. Additionally, genetic liabilities to critically ill COVID-19 were significantly positively associated with 9 immune cells. IgD- CD27- AC and CD27 on IgD+ CD38- unsw mem (memory B cells) were identified as potential mediators of the causal relationship between critically ill COVID-19 and HER2-positive breast cancer. Genetic liability to critically ill COVID-19 is associated with an increased risk of HER2-positive breast cancer possibly through the immune pathway. Future studies are essential to elucidate the mechanisms underlying this causal relationship, aiming to develop therapeutic strategies to mitigate the immune cell-mediated impact on HER2-positive breast cancer risk.

This study aimed to investigate the functional roles and molecular regulatory mechanisms of circular RNAs in the development of glioblastoma multiforme. Differentially expressed circular RNAs were identified by integrating RNA sequencing data and circular RNA microarray data from the Gene Expression Omnibus database. CircAtlas and CircInteractome databases were used to predict microRNAs (miRNAs) interacting with these circular RNAs. Survival analysis of the miRNAs was performed using data from the Chinese Glioma Genome Atlas. The miRTarBase database was used to predict miRNA target genes, followed by the construction of a circular RNA-miRNA-messenger RNA regulatory network specific to glioblastoma multiforme. Functional enrichment analysis was carried out using the DAVID website, and protein-protein interaction networks were created using the Search Tool for the Retrieval of Interacting Genes/Proteins website and Cytoscape. Hub genes were identified, and their expression and prognostic relevance in glioblastoma multiforme were further examined. Four differentially expressed circRNAs and 10 associated miRNAs related to glioblastoma multiforme prognosis were identified. Functional enrichment showed the miRNAs target genes were mainly involved in apoptosis, cell cycle regulation and enriched in cancer-related pathways like mitogen-activated protein kinase and PI3K-Akt. Through the circRNA-miRNA-messenger RNA regulatory network and survival analysis, 3 core genes (core hub genes: catenin beta 1, BCL2, nuclear factor kappa B subunit 1) were identified as significantly downregulated in glioblastoma multiforme and associated with patient survival. This study highlights the potential regulatory roles of circular RNAs in glioblastoma multiforme pathogenesis and their involvement in key molecular pathways. The findings offer a theoretical foundation for understanding glioblastoma multiforme development and may facilitate the identification of novel biomarkers for this aggressive cancer.

Pure erythroid leukemia (PEL) is a rare and highly aggressive subtype of acute myeloid leukemia. Herein, a rare case of de novo PEL with rapid progression harboring EZH2 and TP53 frameshift mutations was reported.

Mitochondria are essential organelles involved in cell metabolism and are closely linked to various metabolic disorders. In this study, we aimed to develop a prognostic model for endometrial cancer (EC) patients based on mitochondria-related genes (MRGs), and to investigate the role of MACC1 in EC. As shown in the graphic summary, we retrieved gene expression and clinical data from open-access databases. To construct a predictive signature, we applied the Lasso Cox regression algorithm to MRGs. The predictive performance, immune features, and anti-tumor response of the mitochondrial signature were evaluated through multiple algorithms. Additionally, expression levels of key genes were validated using quantitative Real-Time PCR and Western Blot. A total of 2030 MRGs were retrieved, and 267 were found to be prognostically relevant. Eight MRGs-MACC1, CMPK2, NDUFAF6, DUSP18, TOMM40L, MT-TP, SAMM50, and MAIP1-were identified to construct a prognostic signature for EC. The MRG signature demonstrated significant associations with drug sensitivity, immune therapy, and immune cell infiltration. Based on comprehensive bioinformatic analysis, MACC1 was identified as the most promising MRG candidate in EC. Systematic experimental validation, including both in vitro and in vivo approaches, demonstrated that MACC1 down-regulation significantly suppressed EC progression, highlighting its potential as a therapeutic target.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are primary liver cancers with overlapping histopathological features, making accurate diagnosis challenging. This study aimed to identify chromosomal abnormalities that could aid in differentiating these cancers using chromosome microarray analysis (CMA). We analyzed ten frozen tumor tissues each of HCC and CCA, identifying distinct patterns of chromosomal gains and losses. HCC exhibited gains in regions 1p36.32, 1q23.3-q24.1, 3q21.3, 4p16.1, 5q31.1, and 11p15.5, and losses in 2p15, 3p11.1-q11.1, 4q12, 5p12-q11.1, 7q11.23, 14q23.2, 17p11.2, 17p13.3, 22q12.1, 22q12.2-q12.3, and 22q13.2. In contrast, CCA showed gains in 5p13.2, 5p14.1, 8p12-p11.23, 8p22, and 19p13.2, and losses in 1q31.1, 1q42.13, 3p25.3, 6p12.1, 6p25.3, and 17q21.33. Heatmap analysis revealed 17 distinct chromosomal regions between the two groups including 2q14.2, 4p16.3, 5q32, 7p14.3, 7p22.1, 7q11.21, 7q11.23, 7q21.3, 7q22.1, 10q21.3, 18q23, 19p13.2, 19q13.2, 21q21.3, 21q22.13, 22q11.21, and 22q12.2. Among these 1p36.32, 19p13.2, and 19q13.2 emerged as potential biomarkers for differential diagnosis. These findings may aid in confirming cases with overlapping histopathological features contribute to the development of diagnostic tools and improved targeted therapies for HCC and CCA.

Krüppel-like factor 4 (KLF4) exhibits both oncogenic and tumor-suppressive effects depending on the type of cancer and cellular context. In T-cell acute lymphoblastic leukemia (T-ALL), KLF4 expression is silenced by promoter methylation, and the induction of KLF4 suppresses the proliferation of T-ALL cells. Therefore, KLF4 is thought to function as a tumor suppressor in T-ALL cells; however, its role in the differentiation of T-ALL cells remains unclear. Here, we show that KLF4 induced T-cell differentiation and apoptosis in TALL-1 cells harboring an activating mutation in NOTCH3. Mechanistically, KLF4 directly downregulated NOTCH3 expression by binding to its promoter, thereby promoting the differentiation of CD4/CD8 double-positive cells into CD4 single-positive cells, with the differentiated cells subsequently undergoing apoptosis. Furthermore, we found that APTO-253, a small-molecule inducer of KLF4, effectively suppressed cell growth in TALL-1 cells by promoting T-cell differentiation followed by apoptotic cell death. These findings suggest a promising strategy for developing novel differentiation therapies for T-ALL with NOTCH3 mutations.

National guidelines recommend next-generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. Non-Hispanic Black men are poorly represented in precision oncology cohorts, and therefore differences in alterations frequencies between non-Hispanic Black and White men remain poorly characterized.

Tumor angiogenesis is essential for further growth and metastasis of solid tumors. However, the mechanisms underlying angiogenesis-related gene expression have yet to be clarified. Here, we discovered RNA-binding proteins monocyte chemotactic protein-induced protein 2 (MCPIP2) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) function as a pair of antagonists that modulate breast tumor angiogenesis by competitively regulating mRNA stability of proangiogenic gene transcripts, including vascular endothelial growth factor A (VEGFA), Erb-B2 receptor tyrosine kinase 2 (ERBB2), interleukin-8 (IL8), C-X-C motif chemokine ligand 1 (CXCL1), and ephrin A1 (EFNA1). Mechanistically, MCPIP2 physically interacted with the stem-loop structures in the 3'-untranslated region of proangiogenic transcripts through its RNase domain to destabilize their mRNAs. Ribosomal proteins might be required for MCPIP2-mediated destabilization of proangiogenic mRNAs. On the other hand, IGF2BP1 can stabilize the proangiogenic mRNAs by binding to the common RNA stem-loop structures. Furthermore, we found that MCPIP2 expression in human breast tumors was repressed, whereas IGF2BP1 expression increased. Lower MCPIP2 expression and higher IGF2BP1 expression in human breast tumors were significantly associated with poor survival of breast cancer patients, respectively. Notably, there was a reversed correlation relationship between MCPIP2, IGF2BP1 expression, and proangiogenic gene expression in human breast tumor samples. Collectively, our results elucidate a novel mechanism by which MCPIP2 and IGF2BP1 competitively modulate the expression of proangiogenic transcripts, which provides new insights into antiangiogenic therapy of breast cancer.

The purpose of current study was to reveal the role of PANoptosis-associated genes in lung squamous cell carcinoma (LUSC) and their potential as prognostic biomarkers. We analyzed RNA-seq data from TCGA-LUSC and GEO datasets to identify differentially expressed genes (DEGs) between LUSC and normal samples, followed by VENN analysis to reveal PANoptosis-related DEGs. Functional enrichment analyses were performed by clusterProfiler package. Distinct LUSC subtypes were identified by consensus clustering based on PANoptosis-related DEGs. Univariate Cox and LASSO regression were utilized to identify key prognostic genes, and a prognostic model was developed based on selected genes. Immune infiltration status was evaluated by CIBERSORT and ESTIMATE algorithms. Expression of key prognostic genes was tested in three LUSC cell lines by RT-qPCR and Western blot. Roles of TLR3 in LUSC progression were determined by functional experiments. A total of 76 PANoptosis-related DEGs were identified, with significant enrichment in apoptosis pathways. The clustering analysis revealed four subtypes, in which survival and immune microenvironment were dramatically different. From the 76 genes, four key prognostic genes (CHEK2, PDK4, TLR3, and IL1B) were identified to establish prognostic risk model, which could reflect the survival status and immune cells composition variations for LUSC patients. Besides, these four genes showed significant correlations with infiltrating levels of various immune cells. TLR3 was identified as a more weighted prognostic risk gene in LUSC. Functional assays demonstrated that genes like TLR3 modulated cell proliferation, migration, and inflammatory responses in LUSC cells. This study highlighted the potential of the four key PANoptosis genes as biomarkers or targets in LUSC, and the risk model based on these four genes provided novel insights to develop personalized treatment strategy for patients with LUSC.

Circulating tumor DNA (ctDNA) can be used as a tool to detect minimal residual disease (MRD) which can provide important prognostic information in diffuse large B-cell lymphomas (DLBCL). Here, we present an ultra-sensitive MRD assay reliant on Phased Variant Enrichment and Detection Sequencing (PhasED-Seq), which leverages phased variants to detect ctDNA.

The epidemic of obesity is a growing concern and is one of the major risk factors for several chronic diseases, including several types of cancers. The correlation of breast cancer with obesity has been extensively studied and involves an interplay of hormonal, metabolic, and genetic factors explored in this review. Inflammation and hormone dysregulation play an important role in promoting a protumorigenic environment through adipose tissue, which is involved in energy storage and functions as an endocrine organ. As a result, various cytokines, primarily proinflammatory in nature, are released, resulting in low-grade inflammation promoting tumor growth. Additionally, obese conditions also induce imbalances in hormones, particularly estrogen and insulin, both of which drive carcinogenesis. Genetic components such as single nucleotide polymorphisms also play critical roles in modulating the correlation between obesity and breast cancer. This review provides a comprehensive overview of various mechanisms underlying obesity and breast cancer incidence and progression.

Neuroblastoma (NB), the common extracranial solid tumor in children, is associated with a poor prognosis, particularly in high-risk patients. MYCN amplification stands as the most prominent molecular hallmark within this high-risk subgroup. However, MYCN protein is considered "undruggable" due to its lack of a conventional enzymatic binding pocket and its predominant nuclear localization, which precludes targeting by standard small-molecule inhibitors or antibody-based therapeutics. Consequently, current therapeutic strategies have achieved limited efficacy against MYCN-driven NB. Notably, MYCN not only orchestrates diverse metabolic reprogramming pathways in tumors but also exerts a pivotal influence on cellular differentiation. To overcome this therapeutic barrier, we seek to elucidate the contribution of purine metabolism to stemness maintenance in MYCN-amplified NBs and to discover novel small-molecule inhibitors capable of inducing differentiation in high-risk NBs.

Hepatocellular carcinoma (HCC) represents a major global health challenge, characterized by its complex immune microenvironment that plays a pivotal role in tumor progression and therapeutic response. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of various biological processes, including gene expression and immune cell function. This review explores the multifaceted roles of lncRNAs in modulating the immune microenvironment of HCC. We discuss how lncRNAs influence the infiltration and activation of immune cells, shape cytokine profiles, and regulate immune checkpoint molecules, thereby affecting the tumor's immunogenicity and response to immunotherapy. Furthermore, we highlight specific lncRNAs implicated in immune evasion mechanisms and their potential as biomarkers and therapeutic targets. By elucidating the intricate interplay between lncRNAs and the immune landscape in HCC, this review aims to provide insights into novel strategies for enhancing immunotherapeutic efficacy and improving patient outcomes.

Chemotherapeutic resistance is a major obstacle to chemotherapeutic failure. Cancer cell resistance involves several mechanisms, including epithelial-to-mesenchymal transition (EMT), signaling pathway bypass, drug efflux activation, and impairment of drug entry. P-glycoproteins (P-gp) are an efflux transporter that pumps chemotherapeutic drugs out of cancer cells, resulting in chemotherapeutic resistance. Several types of long noncoding RNA (lncRNAs) have been identified in resistant cancer cells, including ODRUL, MALAT1, and ANRIL. The high expression level of ODRUL is related to the induction of ATP-binding cassette (ABC) gene expression, resulting in the emergence of doxorubicin resistance in osteosarcoma. lncRNAs are observed to be regulators of drug transporters in cancer cells such as MALAT1 and ANRIL. Targeting P-gp expression using natural products is a new strategy to overcome cancer cell resistance and improve the sensitivity of resistant cells toward chemotherapies. This review validates the inhibitory effects of natural products on P-gp expression and activity using in silico molecular docking. In silico analysis showed that Delphinidin and Asparagoside-f are the most significant natural product inhibitors of p-glycoprotein-1. These inhibitors can reverse multi-drug resistance and induce the sensitivity of resistant cancer cells toward chemotherapy based on in silico molecular docking. It is important to validate that pre-elementary docking can be confirmed using in vitro and in vivo experimental data.

Hepatocellular carcinoma (HCC) represents the third deadliest cancer worldwide with limited treatment options. Immune checkpoint inhibitors (ICIs) have revolutionized HCC therapy, but immune suppression within the tumor microenvironment remains a major challenge. Therefore, in this study, we aimed to define novel ICI molecules arising on T cells during aggressive HCC development.

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and one of the deadliest cancers in humans. Dysregulation of miRNA activity in tumor-associated neutrophils (TANs) in the tumor microenvironment plays an important role in the occurrence and development of LUAD.

Persistent high-risk human papillomavirus (HR-HPV) infection is crucial in transforming cervical intraepithelial neoplasia (CIN) into cervical cancer (CC) by evading immune responses. Additionally, changes in the tumor immune microenvironment (TIME) are increasingly linked to CIN progression to CC.

C-X-C motif chemokine ligand 13 (CXCL13) is a crucial chemokine for the recruitment of immune cells and the formation of tertiary lymphoid structure (TLS) in the tumor microenvironment. However, the relationship between CXCL13 and immune infiltration in cutaneous squamous cell carcinoma (cSCC) remains unclear.