Biparental complete hydatidiform mole (BiCHM) is a rare form of molar pregnancy, frequently associated with familial recurrence, whose mechanism was historically unclear. It is classically diploid with biparental inheritance, but manifests as a complete hydatidiform mole (CHM). Cytogenetic studies suggested a link to maternal mutations in imprinted genes NOD-like receptor family, pyrin domain containing 7 or Kelch helper domain containing 3-like within the oocyte. This case reports a novel gene association.

The incidence of hepatocellular carcinoma (HCC) has risen significantly in recent years, while current diagnostic and therapeutic approaches remain suboptimal. This study aimed to identify novel biomarkers and therapeutic targets to improve early detection and treatment outcomes. We conducted a comprehensive analysis of HCC-related gene expression datasets (GSE101685, GSE14520, and TCGA-LIHC). Differentially expressed genes (DEGs) were identified, followed by weighted gene co-expression network analysis (WGCNA) on the training cohort. A total of 313 shared genes were identified by intersecting 691 DEGs with 1653 genes from the "MEturquoise" module. Functional enrichment analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes, were performed to explore the biological roles of these genes. Subsequently, 109 combinations of 12 machine learning algorithms were applied to identify HCC-specific feature genes. Gene set enrichment analysis and CIBERSORT were used to explore functional pathways and immune infiltration, respectively. Functional analyses revealed that the shared genes were primarily involved in cell cycle regulation and cell division. A total of 96 HCC feature genes were identified through 109 combinations of 12 machine learning algorithms. Among them, 5 novel genes (DNAJC12, KBTBD11, SEC24B, PLSCR4, SH3YL1) with no prior association with HCC were found to have significantly lower expression in tumor samples and were validated for their diagnostic value using receiver operating characteristic analysis. Gene set enrichment analysis further showed their association with immune responses, metabolic processes, and cell cycle regulation. Immune infiltration linked DNAJC12, KBTBD11, and SEC24B to the HCC immune microenvironment. Our study identified 5 previously unreported genes as potential diagnostic biomarkers and therapeutic targets for HCC. These findings provide a new perspective for the molecular characterization and clinical management of hepatocellular carcinoma.

Increasing evidence suggests associations between gut microbiota composition and colorectal cancer (CRC) or hepatocellular carcinoma. However, whether gut microbiota influences metastatic liver cancer (MLC) originating from CRC remains unclear. We performed a bidirectional 2-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies. Gut microbiota data (N = 18,340) from MiBioGen served as exposures. MLC (N = 463,010) and CRC (N = 399,920) datasets were sourced from IEU OpenGWAS. The correlation analysis was primarily conducted using the inverse variance weighted method, which demonstrated reliability as confirmed through sensitivity analysis. Inverse variance weighted estimates indicated that class_Actinobacteria showed an inverse association with MLC (odds ratio [OR] = 0.997, 95% confidence interval [CI]: 0.995-0.999, P = .003), while class_Melainabacteria exhibited a positive association (OR = 1.001, 95% CI: 1.000-1.002, P = .011). For CRC, both class_Actinobacteria (OR = 0.992, 95% CI: 0.986-0.997, P = .005) and order_Bifidobacteriales (OR = 0.991, 95% CI: 0.986-0.997, P = .003) demonstrated inverse associations. Notably, MR estimates revealed that class_Actinobacteria had consistently inverse associations with both MLC and CRC. Reverse MR analysis suggested CRC may increase abundance of family_BacteroidalesS24.7group (OR = 4.178, 95% CI: 3.233-6.304, P = .002), but no significant associations were observed for MLC. This study provides novel evidence supporting potential causal associations between specific gut microbial taxa and the risk of MLC, suggesting a possible protective role of Actinobacteria in the pathogenesis of both MLC and CRC. Further large-scale observational and mechanistic studies are warranted to clarify these relationships.

Lung cancer (LC) is among the most prevalent cancers and is the leading cause of cancer-related mortality. Smoking behavior is the primary etiological factor for LC; however, the potential causal relationship with other risk factors, such as iron status, remains unclear. Currently, there is a significant lack of research investigating the potential causal link between iron homeostasis and LC development. This study employs a 2-sample Mendelian randomization approach to explore the causal relationship between these 2 entities. Data on small cell LC (SCLC) and non-small cell LC (NSCLC) were obtained from the FinnGen R11 database, while data on iron homeostasis, encompassing 4 indicators (ferritin, serum iron, total iron binding capacity, and transferrin saturation) were sourced from the Decode Genetic Sequence Bank. The inverse variance weighted analysis demonstrated a causal genetic association between ferritin levels (β = 0.351; 95% confidence interval = 1.006-2.046; P = .045) and SCLC. The application of Cochran Q test, Rucker Q test, MR Egger intercept, and MR-PRESSO global tests did not reveal any evidence of heterogeneity or pleiotropy (P > .05). In conclusion, from a genetic perspective, elevated ferritin levels are positively correlated with an increased risk of SCLC. Furthermore, no genetic causality was observed between the other 3 indicators of iron homeostasis and either SCLC or NSCLC, nor between ferritin and NSCLC.

The causal links between serum amino acids (AAs) and hepatobiliary neoplasms remain unclear. This study aimed to systematically investigate these associations using Mendelian randomization (MR). Summary-level data on 20 serum AAs were obtained from publicly available genome-wide association studies. Genome-wide association studies data on hepatobiliary neoplasms - including primary liver cancer (PLC), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), gallbladder and extrahepatic bile duct carcinoma, secondary liver cancer, benign liver tumors, and benign tumors of the extrahepatic bile ducts - were derived from FinnGen and 2 UK Biobank-based studies. A meta-analysis was conducted to calculate pooled effect sizes. Inverse variance weighting was the primary method, supplemented by MR-Egger, weighted median, MR.RAPS, maximum likelihood, and MR-PRESSO methods for sensitive analyses. Higher serum methionine was associated with lower risks of PLC (OR = 0.84, 95% CI: 0.72-0.97, P = .021) and HCC (OR = 0.87, 95% CI: 0.80-0.94, P < .001), but not ICC. Alanine increased PLC risk (OR = 1.19, 95% CI: 1.00-1.42, P = .047), with no significant effect on HCC or ICC. No AAs were linked to gallbladder and extrahepatic bile duct carcinoma or secondary liver cancer. For benign tumors, aspartate (OR = 1.13, 95% CI: 1.01-1.26, P = .037), cysteine (OR = 0.72, 95% CI: 0.57-0.92, P = .008), and lysine (OR = 1.49, 95% CI: 1.15-1.93, P = .003) were significantly associated with benign liver tumors or benign tumors of the extrahepatic bile ducts. This study offers robust evidence of causal associations between specific serum AAs and hepatobiliary neoplasms, emphasizing their potential as biomarkers and modifiable targets for early intervention.

Endometrial polyps are common, localized overgrowths of endometrial glands and stroma that protrude into the uterine cavity. These tumor-like lesions can cause symptoms like abnormal uterine bleeding and infertility, and they may undergo malignant transformation. The etiology of endometrial polyps remains largely unknown.

Clonal hematopoiesis of indeterminate potential (CHIP) is a known risk factor for hematologic malignancies (HM), but its distribution and clinical implications across diverse ancestries remain poorly characterized. In this study, we investigated CHIP and its progression to HM in a large, racially diverse cohort from the All of Us Research Program, comprising 245,388 participants. We identified 10,446 CHIP driver mutations in 9,476 individuals. Our analysis revealed clear racial disparities in CHIP prevalence and mutational profiles: African American (AA) individuals had higher odds of CHIP and exhibited distinct mutation patterns compared to White American (WA) individuals. Consistent with prior studies, CHIP was associated with an increased risk of HM, particularly myeloid malignancies. Notably, ancestry influenced the subtype of myeloid malignancy observed; CHIP was more strongly linked to myeloproliferative neoplasms in AA individuals compared with WA individuals. These findings demonstrated significant racial differences in CHIP biology and HM progression, highlighting the need for ancestry-informed approaches to CHIP risk assessment and HM prevention.

Follicular lymphoma (FL) represents the most common subtype of indolent non-Hodgkin's lymphoma. Extranodal involvement (ENI) indicates a poor clinical outcome in patients who received rituximab-based immunochemotherapy. Recent studies indicate that genetic alterations and tumor microenvironment dysregulation drive extranodal dissemination and lymphoma progression. However, the molecular mechanisms underlying ENI in FL remain to be fully elucidated.

This study aimed to evaluate RBM15 gene expression and the potential effects as a biomarker in LUAD progression.

The Rho GTPase-activating protein (RhoGAP) family represents a large and diverse group of proteins that act as key regulators of Rho GTPases, small GTP-binding proteins involved in cellular signaling. Tight regulation of Rho GTPase activity is essential for fundamental biological processes, including cell motility, contractility, growth, differentiation, and development. Despite their biological importance, the roles of RhoGAPs in cancer remain largely undefined.

Lenvatinib resistance significantly limits treatment efficacy in hepatocellular carcinoma (HCC), yet the underlying mechanisms remain poorly understood. This study investigates the role of EZH2 in mediating lenvatinib resistance through ferroptosis regulation, aiming to identify novel therapeutic targets for overcoming drug resistance in HCC.

CAR-T therapy based on the genetic modification of T-lymphocyte receptors is currently a rapidly expanding modern method of treatment of hematological malignancies. In this chapter, the authors review the history of the development of this kind of therapy, principles of the CAR-T therapy product manufacturing, and indications for the use of registered CAR-T therapy products. They also review the perspectives for the expansion of indications using this treatment on the basis of analysis of approved clinical trials. The need for the establishment of effective logistics pathways and the benefits of cryopreservation at different manufacturing steps are reviewed as well. During their 2-year experience, the authors established a system of fluent cooperation between the local licensed Tissue Establishment (TE), CAR-T therapy product manufacturers, the Hospital Pharmacy, and a certified clinical CAR-T therapy centre. The leukapheresis of starting material, its processing, storage, and release for the manufacture took place in the authorized TE. The starting material is usually fresh mature peripheral blood mononuclear cell concentrate, which is sent to the manufacturing site in a chilled (or sometimes cryopreserved) state and the final registered product is sent back in a frozen state. Individual manufacturers use different cold chains. Sometimes the starting material is frozen by the manufacturer and the final manufacture is carried out before the actual administration to the patient as a fresh suspension. However, the most common variant used in registered products is the supply of the final product to the place of the administration in the cryopreserved state.Receipt of final products in the hospital cryobank attached to the TE takes place in cooperation between the TE staff with representatives of the Hospital Pharmacy and is followed by storage in a vapour phase of liquid nitrogen in a separate GMP-compliant container used exclusively for the storage of registered and investigational CAR-T therapy products at a temperature below -150 °C. Before the transport to the Clinical Department, the chain of recipient identity is checked, then the product is transported to the Clinical Department in a dry shipper at temperature below -150 °C. After the second check in the presence of the clinical hematologists, the product is thawed and immediately infused. In the case of the use of investigational products, special attention is paid to meeting specific genetic safety rules in the regimen of genetically modified organisms.

This review will summarize recent research into the diverse biological consequences of splicing factor mutations, and possible therapeutic vulnerabilities uncovered by such mutations, with a dedicated focus on chronic myelomonocytic leukemia.

The intricate tumor microenvironment largely influences chemoresistance in glioblastoma. Cancer-associated fibroblasts (CAFs) that modulate tumor progression have recently been identified as non-tumor stromal cells within the glioblastoma microenvironment. It remains unclear whether CAFs play a role in conferring chemoresistance to glioblastoma. The effects and mechanisms of CAFs on glioblastoma cells under temozolomide (TMZ) treatment are investigated by a series of patient-derived CAFs, orthotopic xenograft mouse models, and glioblastoma organoids (GBOs). Patient-derived cells have a transcriptomic and biomolecular profile of CAFs. CAFs promote temozolomide resistance in glioblastoma in vitro; these findings are consistent with results from intracranial tumor xenografts and GBO models. Mechanistically, CAFs express and secrete a significantly higher C-C motif chemokine ligand 2 (CCL2), which selectively enhances the activation of the ERK1/2 signaling in glioblastoma cells. Pharmacologically disrupting the CCL2-CCR2 axis or MEK1/2-ERK1/2 pathway effectively restores the therapeutic efficacy of temozolomide in glioblastoma cells and patient-derived GBOs. The decreased phosphor-ERK1/2 expression induced by trametinib treatment is also observed in glioblastoma cells following the CCL2-CCR2 axis inhibition. The present study suggests that targeting the CCL2/CCR2/ERK1/2 pathway may help overcome chemoresistance in glioblastomas caused by CAFs.

Long noncoding RNAs (lncRNAs) have been extensively studied for their regulatory roles in gene expression; however, relatively little is known about those specifically associated with super-enhancers (SEs)-genomic elements crucial for maintaining cell identity and function. This study profiles acute promyelocytic leukemia (APL)-specific SE-associated lncRNAs (SE-lncRNAs) using H3K27ac ChIP-seq and RNA-seq data from TCGA and Beat AML cohorts, identifying 44 SE-lncRNAs potentially involved in APL pathogenesis. Among these, we characterized a novel SE-lncRNA, RP11-750H9.5, located upstream of the SPI1 gene encoding the hematopoietic transcription factor PU.1, and designated it as lnc-SPI1U. Functional assays demonstrated that lnc-SPI1U suppressed differentiation, apoptosis and ATRA-induced cell proliferation inhibition, contrasting with the established role of SPI1 in promoting differentiation. Mechanistically, lnc-SPI1U interacted with heterogeneous nuclear ribonucleoproteins HNRNPH1/F, destabilizing SPI1 mRNA. Furthermore, we found that the induction of lnc-SPI1U during myeloid differentiation was dependent on PU.1, which established a feedback loop to fine-tune SPI1 expression at the optimal level for myeloid differentiation. In APL, the PML/RARα fusion protein inhibited PU.1-dependent transactivation of lnc-SPI1U by hijacking the SE region that overlapped with lnc-SPI1U locus. Our study provides mechanistic insight into how SE-lncRNAs contribute to the precise regulation of transcription factor activity during myeloid differentiation.

Cold atmospheric plasma (CAP) has demonstrated anti-proliferative activity in various cancer cells, yet its efficacy against drug-resistant cancer cells remains largely unexplored. This study investigates CAP's potential to restore drug sensitivity in fulvestrant-resistant breast cancer cells. Fulvestrant-resistant T47D/fulR and MCF-7/fulR cell lines were developed through 32-week drug exposure. CAP treatment effectively inhibited growth of both resistant cell lines and restored sensitivity to fulvestrant when used as pretreatment. Genome-wide expression analysis revealed that CAP significantly impacts ribosomal and mitochondrial components during resistance acquisition and treatment. The oncogene CCND3 emerged as a key contributor to drug resistance, being highly upregulated in resistant cells but downregulated following CAP treatment. Functional validation through CCND3 knockdown in both resistant cell lines induced increased apoptosis and extended G1 phase, confirming its critical role in resistance mechanisms. These findings demonstrate that CAP can revert fulvestrant-resistant breast cancer cells to a sensitive state by targeting CCND3 and modulating critical cellular pathways, suggesting promising therapeutic potential for overcoming drug resistance in breast cancer treatment.

Non-small cell lung cancer (NSCLC) remains a major health challenge worldwide, mainly due to the lack of effective early diagnostic biomarkers. Exosome-related genes have recently emerged as potential diagnostic markers due to their roles in tumor progression and immune regulation. This study aimed to identify exosome-related gene signatures as early predictive biomarkers for NSCLC and evaluate their diagnostic and therapeutic significance. We integrated gene expression data from GEO and TCGA databases. Core ExoNSCLC-DEGs were identified using three machine learning methods to construct a NSCLC diagnostic model, and the model was validated using ROC curves, calibration curves, and DCA curves. In addition, immune infiltration analysis, drug enrichment, molecular docking analysis, and regulatory network analysis further explored the potential mechanism of action of ExoNSCLC-DEGs. qRT-PCR experiments verified the reliability of gene expression. We constructed a diagnostic model consisting of six core ExoNSCLC-DEGs (including GPM6A, HYAL1, S100A4, ROBO4, LRRK2, and HBA1). The diagnostic model showed excellent predictive performance in independent cohorts (AUC > 0.98). The calibration curve and DCA curve demonstrated the clinical applicability of the model. Immune infiltration analysis revealed the potential immune effects of some ExoNSCLC-DEGs genes, such as S100A4 and LRRK2, which may play a key role in tumor immune escape. Drug enrichment analysis predicted potential therapeutic compounds, especially sunitinib targeting LRRK2. The regulatory network further identified the key RNA-binding proteins and transcription factors that regulate these biomarkers. qRT-PCR experiments verified the reliability of the expression of ExoNSCLC-DEGs in bioinformatics analysis. The diagnostic model based on the six ExoNSCLC-DEGs has strong diagnostic performance and clinical applicability. In-depth research on ExoNSCLC-DEGs provides new insights into the pathogenesis of NSCLC and provides new directions for subsequent research.

Oxaliplatin resistance remains a major challenge in colorectal cancer (CRC) treatment. We investigated the FBXL5/IREB2/TFRC axis in ferroptosis-mediated resistance reversal. Bioinformatics analysis identified IREB2 as co-expressed in oxaliplatin resistance and ferroptosis pathways. Clinical samples revealed elevated iron metabolism in resistant CRC tissues. In vitro, FBXL5 knockdown in oxaliplatin-resistant cells (HCT-116/OXA) upregulated IREB2/TFRC, increased Fe²⁺/MDA, and reduced viability/proliferation. Combining oxaliplatin with ferroptosis inducer Erastin enhanced cell death, reversed by ferroptosis inhibitor Ferrostatin-1. Our findings demonstrate that targeting FBXL5 disrupts iron homeostasis, triggers ferroptosis, and overcomes oxaliplatin resistance in CRC.

Colorectal cancer (CRC) is a leading causes of cancer-related mortality worldwide. Dysregulated expression of specific genes and non-coding RNAs contributes to CRC progression. This study investigated the expression and clinical relevance of CEACAM6, HOXA-AS3, and miR-29a in CRC, combining experimental data with bioinformatics analysis to assess their diagnostic and prognostic value. Tissue samples from 68 CRC patients (tumor and adjacent normal) were analyzed for CEACAM6, HOXA-AS3, and miR-29a expression by real-time PCR. Bioinformatics validation using TCGA, GEPIA, and ENCORI databases assessed expression, interactions, and assess clinical associations. CEACAM6 and miR-29a were significantly upregulated, while HOXA-AS3 was downregulated in CRC tissues compared to normal counterparts. Notably, miR-29a also showed elevated expression levels in patient serum samples (p < 0.05). Among the examined markers, CEACAM6 expression varied significantly with tumor differentiation status (p < 0.05). Serum levels of IL-6 were significantly increased in CRC patients (p < 0.05). Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy for miR-29a (AUC = 0.918). A significant positive correlation was observed between miR-29a expression in serum and tumor tissue (p = 0.038). Additionally, in silico analysis suggested regulatory interactions between HOXA-AS3 and the mRNAs of CEACAM6 and IL-6. CEACAM6, HOXA-AS3, and miR-29a may serve as promising biomarkers for early detection and prognosis of CRC. Integrating molecular profiling with bioinformatics validation provides a robust approach to uncover clinically relevant targets in CRC. The correlation between serum and tumor tissue miR-29a expression highlights its potential utility in liquid biopsy approaches for CRC.

Emerging evidence supports the role of type 2 diabetes (T2D) mellitus as a risk factor for cancer progression. In this study, we investigated and identified biomarkers related to diabetes and pancreatic ductal adenocarcinoma (PDAC) using systems biology to understand better the molecular landscape of PDAC and its connections with T2D.RNA-seq data related to blood samples of diabetes and pancreatic cancer were analyzed using bioinformatics tools in the Galaxy platform. After differential expression analysis using the DESeq2, the co-expression network associated with T2D and PDAC data was reconstructed using the WGCNA. Then, by visualizing the protein-protein interaction network in modules specifically related to T2D and PDAC, the key genes involved in these two diseases were identified, and their interaction network with long non-coding RNAs was reconstructed. Finally, the results of bioinformatics analysis were verified by qPCR in four groups, including T2D, PDAC, PDAC-T2D, and control groups.In this study, 1905 and 18,558 genes with significant differential expression were identified in the data of T2D and PDAC, respectively (|logFC| > 0.58, adj. p value < 0.05). The WGCNA showed 32 and 20 co-expression modules in diabetes and pancreatic cancer data, respectively. Among these, 303 genes were co-expressed, related to diabetes and pancreatic cancer. Based on the protein-protein interaction pattern, five hub genes were identified (using the CytoHubba Cytoscape plugin and the Maximal Clique Centrality (MCC) parameter). Finally, the co-expression network was reconstructed between these five genes and other lncRNAs. The qPCR showed that the expression of the CEBPZ gene was significantly increased in the blood samples of the diabetic (log2FC = 1.163, adj. p value = 0.0006), pancreatic cancer (log2FC = 3.22, adj. p value < 0.0001), and pancreatic cancer-diabetic (log2FC = 2.73, adj. p value < 0.0001) groups compared to the control group.For the first time, this study suggested that CEBPZ expression may serve as a diagnostic biomarker for assessing PDAC in individuals with T2D, given its differential expression in this specific cohort.