Diagnosing papillary thyroid carcinoma (PTC) remains challenging, particularly due to limitations in fine-needle aspiration biopsy (FNAB), which yields up to 10% nondiagnostic results. The objective of this study was to evaluate the diagnostic and prognostic potential of four candidate microRNAs (miR-21, miR-31, miR-187-3p, and miR-200a-5p) in PTC from multinodular goiter (MNG) and normal. Fresh tissue samples from PTC and MNG patients were analyzed using quantitative RT-PCR, followed by ROC analysis to assess diagnostic accuracy and correlation with clinical, histopathological, and hormonal parameters. Compared to normal tissue, miR-21 and miR-187-3p were significantly upregulated in PTC, while miR-31 and miR-200a-5p were downregulated. MNG samples showed similar but less pronounced trends. All four miRNAs differed significantly between PTC and MNG. ROC analysis revealed strong diagnostic performance, particularly for miR-187-3p (AUC = 0.937) and miR-21 (AUC = 0.914), with their combination achieving an AUC of 0.968. Expression levels correlated with age, tumor stage, surgical status, and thyroid hormones (TSH, ATG, TG), highlighting novel regulatory patterns. This miRNA panel offers promising diagnostic value and insight into PTC pathogenesis, suggesting potential for non-invasive diagnostics and targeted therapies.

Prostate cancer (PC) remains a leading cause of cancer-related mortality in men, with recurrence contributing significantly to poor outcomes. Its molecular heterogeneity complicates effective risk stratification. We evaluated Sig27, a novel 27-gene panel, across 13 bulk RNA-seq datasets (n = 3,133 tumors) and 6 single-cell RNA-seq (scRNA-seq) datasets (n = 53 patients). Sig27 expression was elevated in PC compared to normal tissue and further increased in high-grade Gleason tumors, node-positive, and recurrent tumors. Sig27 demonstrated recurrence prediction comparable to Oncotype DX, with strong enrichment in immune regulatory pathways. To further investigate immune associations, we developed SigIC, a 22-gene immune checkpoint panel. Sig27 showed strong correlations with SigIC and individual immune checkpoints (e.g., HAVCR2, CD96, TIGIT) in both primary and metastatic PC. In scRNA-seq data, Sig27 was enriched in tumor-associated monocytes/macrophages (TAMs) and endothelial cells. We identified five key Sig27 genes - TFEC, FPR3, NOD2, LAMP3, and MCTP1 - and constructed Sig27IMG, a multigene panel formed by these five genes, and demonstrated their robust correlations with immune checkpoints and their strong enrichment in TAMs and endothelial cells. Sig27IMG strongly predicted PC recurrence and was dominantly expressed in TAMs, dendritic cells, and endothelial cells across 26 cancer types (n = 386 patients) in scRNA-seq studies and 17 cancer types (n = 5,672 patients) in bulk RNA-seq investigations. Notably, Sig27IMG stratified patients with a poor prognosis risk in these 17 cancer types. In summary, Sig27 and its derivative panel, Sig27IMG, offer a robust assessment of PC recurrence, highlighting immunosuppressive features mediated by TAMs, dendritic cells, and endothelial cells across multiple cancer types.

Multiple myeloma (MM) remains an uncurable hematologic cancer due to neoplastic proliferation of plasma cells. The role and detailed mechanisms of Ubiquitin-Specific Protease 4 (USP4) in MM remain to be clarified. Cell viability and apoptosis were evaluated by CCK-8 and TUNEL. Molecular expression was determined by RT-qPCR, Western blotting, and immunohistochemistry. The morphology of endoplasmic reticulum (ER) was observed by ER tracker-red. The protein interaction and ubiquitination level were evaluated by Co-IP. The binding of myocyte enhancer factor 2A (MEF2A) to the USP4 promoter was confirmed by ChIP and dual luciferase reporter assay. The in vivo growth of MM was monitored by subcutaneous xenograft experiments. USP4 knockdown suppressed MM cell proliferation and triggered ER stress and apoptosis, whereas USP4 overexpression resulted in the opposite effect. Mechanistically, USP4 enhanced nuclear receptor subfamily 4 group A member 1 (NR4A1) protein stability by inhibiting its ubiquitination. MEF2A bound to the USP4 promoter to activate its transcription and expression. The promotive effect of sh-USP4 or sh-MEF2A on ER stress and apoptosis of MM cells was counteracted by NR4A1 or USP4 overexpression. MEF2A deficiency restrained in vivo MM growth by activating ER stress and apoptosis through modulation of the USP4/NR4A1 pathway. MEF2A activates USP4 to repress ER stress and apoptosis of MM cells via deubiquitination of NR4A1, thus favoring MM progression. Our findings identify USP4 as an attractive intervention target for MM therapy.

As neuroblastoma is a highly heterogeneous pediatric solid tumor, it is essential to select appropriate reference genes to compare the concentration of circulating free DNA (cfDNA) between patients with neuroblastoma and healthy individuals. cfDNA was extracted from peripheral blood and quantified using quantitative Polymerase Chain Reaction (qPCR). The stability of candidate reference genes (RGs) was analyzed using the ΔCt method, geNorm, NormFinder, and BestKeeper. The results from these four algorithms were integrated using the RefFinder tool to generate a comprehensive stability ranking and assess the stability of these candidate RGs across different sample groups. Alpha hemoglobin stabilizing protein (AHSP) and Hypoxanthine-Guanine Phosphoribosyltransferase 1 (HPRT1) exhibited the highest stability, whereas Beta-2-microglobulin(B2M) and HBS1-like protein(HBS1L) demonstrated the lowest stability. qPCR of cfDNA from patients with neuroblastoma revealed differences in the stability of various reference genes. Prioritizing reference genes with better stability may facilitate more accurate detection of intergroup differences in the samples.

The integration of regional hyperthermia into the multimodal treatment of patients with localized high-risk soft tissue sarcomas has been shown to improve overall survival. However, specific effects on the tumors' genetic makeup and biology are largely unknown. Since clonal selection of malignant cells capable of thermoresistance might contribute to disease progression, a better understanding of the induced tumor evolution could inform strategies for improving treatment efficacy.

Olaparib is approved for the treatment of germline BRCA mutant (gBRCAm) high-risk early breast cancer (eBC) following treatment with neoadjuvant or adjuvant chemotherapy. The potential long-term outcomes of widespread germline BRCA testing and treatment with olaparib in the US have not been quantified.

Protein disulfide isomerase family A member 4 (PDIA4), a member of the protein disulfide isomerase family, has been associated with the progression of cancer. Nevertheless, its specific function in oral squamous cell carcinoma (OSCC) is not yet well understood.

Extracranial metastasis of IDH-wildtype glioblastoma is very rare and poorly understood at the molecular level. We report a case of FGFR3::TACC3 fusion IDH-wildtype glioblastoma in a 61-year-old male, whose preoperative blood sample showed highly aberrant cfDNA fragmentation patterns, which could be suggestive of early systemic dissemination, undetected by standard-of-care imaging of his body. Eleven months post-resection and adjuvant therapy, he developed widespread extracranial metastases. Comprehensive molecular profiling of matched primary and metastatic tumors revealed broadly conserved genomic, transcriptomic, and copy number landscapes, with the metastasis harboring an additional ERCC6 deletion and enriched expression of receptor tyrosine kinase signaling genes. These findings provide rare insight into the genetic continuity and evolution underlying IDH-wildtype glioblastoma metastasis.

In many cancer patients, distant metastases develop after years of dormancy. Understanding how disseminated tumor cells (DTCs), which are often found in proximity to the microvasculature, remain dormant and what regulates their reactivation is one of the major challenges in tumor biology. In a screen for endothelial secreted and plasma membrane proteins able to regulate tumor cell dormancy, we identified the transmembrane protein platelet and endothelial aggregation receptor 1 (PEAR1). Human and murine endothelial cells lacking PEAR1 lost the ability to promote dormancy of different tumor cells, and the extracellular part of PEAR1 was able to rescue this effect. Similarly, in mice lacking PEAR1 in endothelial cells, tumor cell dormancy in the lung was reduced and tumor metastasis was increased. We found that PEAR1 induces tumor cell dormancy by binding lysyl oxidase like 2 (LOXL2) and cathepsin D (CTSD), which both inhibit tumor cell dormancy and promote tumor growth and metastasis. Tumor cells with suppressed CTSD expression showed increased dormancy and decreased metastatic potential in vivo. Our data identify a mechanism underlying tumor cell dormancy and suggest CTSD and LOXL2 as targets for approaches to promote dormancy.

This study aimed to investigate the potential prognostic role of nitrogen permease regulator-like 2 (NPRL2) gene expression in predicting biochemical recurrence (BCR) following robot-assisted radical prostatectomy (RARP).

Gastric cancer is a highly aggressive malignancy with poor prognosis and low survival rates. The Fragile X Mental Retardation 1 (FMR1) gene has been implicated in the development and progression of various tumors, but its role in gastric cancer remains unclear.

Abnormal one-carbon metabolism has been reported by observational studies to contribute to an increased risk of polycystic ovary syndrome (PCOS) and undesirable reproductive outcomes in women with PCOS. However, the underlying causal associations remain uninvestigated. This study aims to assess the independent causal links between essential substrates, enzymes and cofactors involved in one-carbon metabolism and PCOS, using bidirectional two-sample Mendelian randomization (MR) and Multivariable MR.

Metastasis is the most common cause of colorectal cancer (CRC)-related death. Neutrophil extracellular traps (NETs) promote tumor progression and distant metastasis. This study aimed to explore the role of NETs in CRC liver metastasis. Through analysis of publicly available single-cell transcriptome sequencing databases, in vitro experiments and nude mouse liver xenograft model experiments, we revealed that NETs promote CRC metastatic progression. Using scRNA-Seq technology, we showed that NETs marker expression was higher in metastatic lesions than in primary tumors. NET marker expression was high in colorectal cancer tissues and correlated with advanced tumor pathological grade. In addition, treatment with NETs enhanced the proliferation, migration and invasion of CRC cells in vitro by inducing EMT, as indicated by downregulation of E-cadherin and upregulation of N-cadherin and Vimentin. Cell-cell communication analysis revealed that NETs are related to the PI3K/AKT pathway and regulate the expression of LDHA, a key enzyme in glucose metabolism. In vitro, treatment with NETs promoted LDHA production and cell invasion and migration in CRC, while knockdown of LDHA suppressed EMT. Further, inhibition of LDHA expression or NET formation effectively inhibited NET-induced liver metastasis. In summary, this study elucidates the mechanism by which NETs regulate LDHA expression to promote CRC liver metastasis.

Lung adenocarcinoma (LUAD) is characterized by poor prognosis and limited treatment options. The homologous recombination factor with OB-fold (HROB) is reportedly associated with DNA repair, playing an essential role in a variety of cancers. However, the functional impact, clinical relevance, and underlying mechanisms of HROB in LUAD remain elusive, prompting this study to comprehensively characterize its expression profile and pathogenetic contributions.

To analyze the lipidomic profile of ESCC patients, link changes in cancer lipid metabolism to gene expression changes, and provide new insights into the diagnosis and treatment of ESCC patients in the Kazakh Xinjiang ethnic group.

The clinical heterogeneity observed in chronic lymphocytic leukemia (CLL) is largely attributed to diverse underlying genomic alterations. Fluorescence in situ hybridization (FISH) remains the standard cytogenetic technique but is limited to predefined loci. As a genome-wide approach, optical genome mapping (OGM) facilitates the identification of structural variants (SVs), such as copy number variations (CNVs), offering a broader genomic perspective. This study was designed to compare the findings of FISH and OGM in a cohort of CLL patients. By integrating these two cytogenetic approaches, we sought to evaluate the potential of OGM in detecting additional or cryptic genomic alterations that may impact prognosis and therapeutic decision-making.

Hepatocellular carcinoma (HCC) is a prevalent and deadly cancer worldwide, characterized by poor prognosis, multiple therapeutic challenges, and considerable heterogeneity among patients with diverse etiologies. This heterogeneity contributes to resistance to chemotherapies and molecularly targeted agents, posing a major therapeutic challenge. Therefore, there is an increasing need for treatment strategies targeting HCC across various biological processes. miR-192-5p has been reported to function as a tumor suppressor in HCC, but its target genes remain largely unknown. In this study, we aimed to identify novel target genes of miR-192-5p in HCC using RNA sequencing and 3'-untranslated region analysis. As a result, eight genes-EFEMP1, DLG5, PPP1CA, FAM234B, RPL4, SEC23B, ELOVL1, and CBFB-were identified as novel target genes of miR-192-5p, all of which were significantly upregulated in HCC tissues. Notably, three genes-CBFB, SEC23B, and RPL4-were also validated as novel targets of miR-194-5p, which clusters with miR-192-5p. These findings suggest that miR-192-5p exerts its tumor-suppressive function by inhibiting a novel gene network that may contribute to HCC progression. This study provides new insights into the molecular mechanisms underlying HCC heterogeneity and highlights miR-192-5p-regulated networks as potential therapeutic targets for HCC.

The vast majority of recurrent somatic mutations arising in tumors affect protein-coding genes in the nuclear genome. Here, through population-scale analysis of 14,106 whole tumor genomes, we report the discovery of highly recurrent mutations affecting both the small (12S, MT-RNR1) and large (16S, MT-RNR2) mitochondrial RNA subunits of the mitochondrial ribosome encoded within mitochondrial DNA (mtDNA). Compared to non-hotspot positions, mitochondrial rRNA hotspots preferentially affected positions under purifying selection in the germline and demonstrated structural clustering within the mitoribosome at mRNA and tRNA interacting positions. Using precision mtDNA base editing, we engineered models of an exemplar MT-RNR1 hotspot mutation, m.1227G>A. Multimodal profiling revealed a heteroplasmy-dependent decrease in mitochondrial function and loss of respiratory chain subunits from a heteroplasmic dosage of ~10%. Mutation of conserved positions in ribosomal RNA that disrupt mitochondrial translation therefore represent a class of functionally dominant, pathogenic mtDNA mutations that are under positive selection in cancer genomes.

Due to a high rate of recurrence coupled with resistance towards modern therapies, colorectal cancer (CRC) is considered as the third cause of cancer-related death worldwide. Gemini curcumin (Gemini-Cur) is one of the last nanoformulation of curcumin with significant toxicity on colorectal cancer. Herein, we aimed to unravel the modulated lncRNAs, related mRNAs and downstream cellular pathways in Gemini-Cur treated HT-29 colorectal cancer cells. 9805 lncRNAs were found to be differentially expressed in nanocurcumin-treated cancer cells versus non treated group. The top 20 lncRNAs were selected for further studies and, 14,472 co-expression relationships between these RNAs and 70,711 mRNAs were identified. Among top 20 lncRNAs, tumor-suppressive C8orf31 and ARHGAP5-AS1, as well as oncogenic XIST, FTX, and NEAT1 were the most notable due to their involvements in cancer-related cellular pathways. Functional enrichment analyses demonstrated that the modulated lncRNAs and their targets are involved in cell cycle, p53 signaling, translation, and helicase activity pathways. In conclusion, our study elucidated new molecular mechanisms of nano-curcumin in the regulation of lncRNA expression and the discovery of potential targets in therapeutic interventions for CRC. More studies are needed to confirm the therapeutic implications of these findings.

Insulin-like growth factor-1 (IGF-1) is associated with prostate cancer (PCa) development and lethality and exhibits immunosuppressive properties in other models. We investigated IGF-1's tumor-intrinsic immune effects in PCa to understand mechanisms underlying its poor immunotherapy response. Transcriptional profiling of human (DU145, 22Rv1) and murine (Myc-CaP) PCa cells revealed that IGF-1 suppresses cytokine signalling, antigen processing and presentation, and additional immune regulatory pathways. We further examined the expression of components involved in cancer cell recognition and immune evasion: the antigen processing machinery and PD-L1 checkpoint. IGF-1 downregulated key elements such as transporters associated with antigen processing (TAPs), endoplasmic reticulum aminopeptidase-1 (ERAP-1), and Class I β2-microglobulin, without significantly altering Class I allele expression. These changes were associated with reduced surface presentation of Class I complexes on Myc-CaP cells, suggesting disrupted peptide transport, processing, and/or presentation. In contrast, IGF-1 upregulated the immune checkpoint CD274 (PD-L1) via IGF receptor/AKT/ERK-dependent signalling. Analysis of TCGA Firehose Legacy PCa data showed higher CD274 expression in tumors with elevated IGF1 and IGFBP5. Multiplex immunofluorescence in primary PCa confirmed increased PD-L1 in patients with high serum IGF-1, supporting its role in immune evasion. Overall, these findings reveal a novel IGF-1-driven immunosuppressive mechanism that may underlie PCa's resistance to immunotherapy.