Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, and the treatment options are limited. Growing evidence shows that long non-coding RNAs (LncRNAs) encode peptides, suggesting that lncRNAs-derived peptides may play a role in HCC progression and explore their potential as therapeutic targets.

Hepatocellular carcinoma (HCC) is becoming increasingly prevalent as a non-AIDS-defining cancer closely tied to chronic HIV infection. It is associated with increased secretion of inflammatory cytokines, immune system dysfunction, and alterations in mitochondrial function. The objective of this study was to investigate the levels of cytokine secretion and mitochondrial DNA (mtDNA) deletion in people living with HIV (PLWH) compared with individuals diagnosed with HCC without HIV.

Breast cancer is the most common malignant tumor among women globally, with incidence and mortality rates ranking first among female cancers. Mitochondrial dysfunction plays a crucial role in the occurrence, development, and metastasis of breast cancer, but the specific mechanisms remain unclear. This study aims to explore the mechanisms and prognostic value of the mitochondrial-related gene PARK7 in breast cancer.

Hypoxia is a hallmark of solid tumors and gives rise to the glucose metabolic reprogramming of cancers. Peptides and proteins encoded by circular RNAs (circRNAs) are identified as pivotal mediators in the malignant progression of tumors. Nonetheless, proteins encoded by hypoxia-related circRNAs in pancreatic cancer (PC) remain uncharacterized and poorly understood.

Ovarian cancer is a lethal disease with high mortality due to late diagnosis, recurrence, and chemotherapy resistance. There is an urgent need for better diagnostic and therapeutic strategies. Recently, protein post-translational modifications (PTMs) have gained significant attention for their role in the onset, progression, and treatment of ovarian cancer. PTMs (including phosphorylation, ubiquitination, methylation, ADP-ribosylation, and others) significantly influence tumor cell proliferation, metastasis, and drug resistance by modulating cellular signal transduction, DNA repair mechanisms, and metabolic processes. PARP inhibitors block the active site of PARP1 in BRCA-mutant ovarian cancer, disrupting ADP-ribosylation, inducing apoptosis in cancer cells, and extending progression-free survival. However, the emergence of drug resistance, such as BRCA reversal mutations, and the insufficient specificity of targets remain significant limitations to therapeutic efficacy. Strategies targeting other modification pathways, such as ubiquitination and methylation, provide promising options for expanding treatments. Combination therapies, like integrating PARP inhibitors with chemotherapy or immunotherapy, and precision medicine also show potential to overcome therapeutic challenges. This article systematically examines the pivotal role of PTMs in ovarian cancer pathogenesis, outlines therapeutic strategies and associated challenges in targeting PTMs, and offers a comprehensive overview with strategic guidance for future research.

Early-stage Luminal A breast cancer generally has a favorable prognosis, yet some patients experience recurrence, presenting a challenge in understanding the underlying genetic factors. This study aimed to identify genetic mutations associated with recurrence in early-stage Luminal A breast cancer patients through whole-exome sequencing (WES).

Adrenocortical hyperplasia is an autosomal recessive disorder characterized by congenital metabolic dysfunction, resulting in endocrine disturbances and abnormal sexual development (such as female masculinity), requiring lifelong hormonal therapy. Notably, non-classical congenital adrenal hyperplasia (NCCAH) exhibits clinical manifestations resembling polycystic ovary syndrome (PCOS), yet their therapeutic approaches in fertility treatment differ substantially. Importantly, NCCAH carries the risk of delivering offspring with severe adrenal hyperplasia, which presents far graver consequences than PCOS. Accurate differentiation between these two conditions is therefore crucial for proper clinical management. However, to date, no large-scale screening studies have been conducted to investigate the prevalence and carrier status of NCCAH among PCOS populations.

The lysyl oxidase family is a group of copper-containing amine oxidases involved in the remodeling of the extracellular matrix, and regulates cell signaling, metabolism, organ development, and immunity by modifying the cellular matrix. Among them, LOXL3 had been shown to regulate the proliferation, migration, and invasion of breast, colorectal, lung, melanoma, and gastric cancers. Differential expression of LOXL3 in tumor affects tumor progression by modulating immune microenvironment, where LOXL3 plays a role in regulating immune cell infiltration, immune checkpoints, and the establishment of tumor drug resistance. Here, we summarize the structure, mechanism, and functional role of LOXL3 in tumor and tumor immune microenvironment. Further, we explored strategies to improve the immunotherapy efficacy by targeting LOXL3 in tumor. Based on its properties in immunity, we explored strategies to improve the immune efficacy of LOXL3 in immunotherapy.

Endometrial carcinoma is among the most common female malignancies. Many prognostic factors of endometrial carcinoma are proposed to predict survival in endometrial carcinoma patients. Cyclin D1 has been implicated in many malignancies including gastrointestinal and breast carcinoma. To correlate the immunohistochemical expression of Cyclin D1 in endometrial carcinoma with the different clinicopathological parameters. Forty-five cases of endometrial carcinoma with different histological subtypes and grades were included. Cyclin D1 expression was immunohistochemically tested. For each case, the predominant intensity was recorded, the density (as the percentage of positively stained cells irrespective of intensity) and H-score were recorded. Moreover, immunohistochemical staining for p53 and mismatch repair (MMR) proteins was done. All included cases showed different degrees of Cyclin D1 expression. Cyclin D1 expression was predominantly strong in 20 cases (44.4%). The density ranged from 1 to 90% and the H-score ranged from 1 to 270. Both H-score and density correlated significantly with MMR deficiency (p = 0.024 & p = 0.043 respectively) with different cut-offs (> 65 and >  20 respectively). Similarly, a predominant strong intensity correlated significantly with MMR deficiency (p = 0.023). Only Cyclin D1 density correlated significantly with FIGO grade (p = 0.036). At the assigned cut-off, H-score correlated significantly with the overall survival (p = 0.023). When predominantly moderately expressed, Cyclin D1 correlated significantly with recurrence free survival (p = 0.038). Cyclin D1 expression may predict MMR status and correlates with both overall survival and recurrence free survival in endometrial carcinoma.

Serotonin plays a regulatory role in cancer progression, but its role in glioblastoma growth, the most frequent and aggressive malignant brain tumor, is unclear. The expression and cellular distribution pattern of key components of the serotoninergic system in glioblastoma cells have not been fully characterized. Using transcriptomic analysis of public datasets, we identified subtype-specific expression pattern of serotonin-related genes. The biosynthetic enzymes tryptophan hydroxylase 1 and 2 and the serotonin transporter (SERT/SLC6A4) were enriched in the classical (CL) and proneural (PN) molecular subtypes, whereas monoamine oxidase-A expression was uniformly distributed across all subtypes. Notably, the serotonin receptors HTR1D and HTR7 transcripts were upregulated in ME and CL tumors. Additionally, by using RT-qPCR and immunofluorescence, we observed a differential expression and intracellular distribution pattern of all serotoninergic system elements in human glioblastoma-derived cell lines. Our findings demonstrate the differential expression and cellular localization of the serotoninergic elements in human glioblastomas and suggest their potential participation in their progression.

Oral cancer has high mortality and recurrence rates. This is attributed to resistance to the process of regulated cell death and resistance to radiotherapy and chemotherapy. Oral squamous cell carcinoma (OSCC) accounts for the majority of oral cancers. Its prognosis varies with the site, clinical stage, and histological grade of the tumor. Owing to the variation in the biological behavior of OSCC, the existing prognostic parameters have some limitations in terms of providing precise information on prognosis. The remarkable biological effects of vitamin D against oral cancer have been documented in various studies. These include antiproliferative and anti-invasive effects, inhibition of angiogenesis, stimulation of mutual adherence of cells, and induction of apoptosis in OSCC. Furthermore, vitamin D increases the sensitivity of OSCC tumor cells to chemotherapy. This phenomenon has been observed in tumors that are resistant to chemotherapy. These findings indicate that the biological effects of vitamin D may provide significant prognostic value in oral cancer patients. In addition, the administration of vitamin D improves the quality of life of patients with inoperable oral cancer lesions in addition to the reported increase in tumor sensitivity to chemotherapy. A low level of vitamin D is associated with increased oral cancer risk. A high frequency of vitamin D deficiency and pleomorphism of the VDR have been reported in oral cancer patients. Poorly differentiated and aggressive OSCCs exhibit more CYP24A1 and VDR polymorphisms and less CYP27B1. Determination of the serum level of vitamin D and identification of VDR, CYP24A1, and CYP27B1 in oral cancer cells may be of significant prognostic value in oral cancer patients and may significantly improve the management of head and neck cancers.

This study investigates the functions of chromobox 6 (CBX6) in esophageal squamous cell carcinoma (ESCC) and delves into its functional mechanisms. The bioinformatics insights suggested that CBX6 was overexpressed in ESCC and linked to dismal prognosis. Cbx6 knockdown was induced in mouse mEC25 cells. This procedure curbed the proliferation and migration of mEC25 cells and reduced exhaustion of the co-cultured CD8+ T cells. In vivo, Cbx6 knockdown in mEC25 cells reduced tumorigenesis while enhancing immune activity in mice. Further experiments showed that CBX6 reduced CD8+ T cell cytotoxicity by secreting C-C motif chemokine ligand 8 (CCL8) and promoting monocarboxylate transporter 4 (MCT4)-mediated lactate transport. Regarding the mechanism, CBX6 regulated the expression of SWI/SNF related BAF chromatin remodeling complex subunit D1 (Smarcd1) to modulate chromatin remodeling, thus promoting transcription of Ccl8 and Slc16a3 (encoding MCT4). Smarcd1 overexpression restored metabolic activity in mEC25 cells, reduced activity of co-cultured CD8+ T cells, and promoted tumorigenesis in vivo. Tissue microarrays analysis suggested that CBX6 and SMARCD1 were linked to immunosuppression and poor prognosis in clinical samples. In conclusion, this study suggests that CBX6 induces CD8+ T cell exhaustion and tumor development in ESCC through SMARCD1-mediated CCL8 secretion and lactate efflux.

Atypical teratoid/rhabdoid tumors (ATRTs) are rare, aggressive Central nervous system (CNS) tumors in young children with poor prognosis. Molecular subgrouping (ATRT-TYR, ATRT-SHH, ATRT-MYC) is crucial for understanding biology, guiding treatment, and predicting outcomes. This study assesses immunohistochemistry (IHC) as a surrogate for molecular subgrouping and is the second study to analyze histomorphological patterns across subgroups.

This study aims to identify core genes closely associated with the diagnosis and prognosis of colorectal cancer (CRC) using transcriptome-based meta-analysis approach and machine learning algorithms. Nine CRC datasets from the GEO database were integrated for differential gene expression analysis and WGCNA to identify key genes. Ninety-six combinations of machine learning algorithms were employed to further refine the selection of core genes and validate their diagnostic performance. Functional enrichment, molecular pathways, and associations with the immune microenvironment of core genes were analyzed using GSEA, CIBERSORT, and ssGSEA. Drug sensitivity predictions were performed to evaluate the impact of core genes on CRC drug response, and molecular docking simulations were used to identify candidate compounds targeting the core genes. A total of 26 core genes were identified, among which the high expression of the SACS gene was significantly associated with poor prognosis, advanced stage, and specific pathological subtypes in CRC patients. GSEA revealed that high SACS expression prominently activates cell cycle regulatory pathways and immune pathways while suppressing metabolic pathways. Furthermore, in vitro experiments demonstrated that SACS is highly expressed in CRC cells and that its knockdown significantly inhibits CRC cell proliferation, suggesting its functional role in tumor growth. Immune analysis showed that high SACS expression was positively correlated with activated NK cells but negatively correlated with Tregs and resting NK cells. Drug sensitivity analysis indicated that high SACS expression reduces sensitivity to oxaliplatin. Molecular docking identified coumestrol and quercetin as potential compounds targeting SACS. SACS promotes CRC progression by regulating cell cycle pathways, the immune microenvironment, and metabolic pathways. And it may serve as a potential therapeutic target for CRC.

Genome-wide association studies (GWAS) have identified numerous single-nucleotide polymorphisms (SNPs) associated with various diseases, including cancer. However, the mechanisms by which these SNPs contribute to disease susceptibility remain largely unclear. While recent studies have explored the transcriptional impact of disease-associated SNPs, their role in post-transcriptional regulation has been less extensively investigated. In this study, we investigated whether cancer-associated SNPs influence gene expression by altering N6-methyladenosine (m6A) RNA methylation. We collected GWAS-identified SNPs across nine cancer types and integrated these with matched tumor and normal m6A RNA immunoprecipitation sequencing (m6A-seq) and RNA sequencing (RNA-seq) datasets. We first identified differentially methylated m6A sites and assessed whether cancer-associated SNPs were enriched within these regions. These analyses revealed that cancer-associated SNPs were significantly enriched within hypermethylated m6A regions in colon cancer. Integrative analysis revealed that SNPs enriched in m6A-modified regions are associated with altered gene expression and RNA splicing, suggesting that m6A methylation mediates the post-transcriptional impact of genetic variants. Experimental validation further confirmed altered gene expression following ALKBH5 knockdown, consistent with patient-derived data. Collectively, our findings support a novel mechanistic connection between genetic variants and RNA methylation-driven transcriptomic regulation in colorectal cancer, underscoring the epitranscriptome as a potential axis of oncogenic control.

Microarray technology has revolutionized cancer genomics by enabling the simultaneous analysis of thousands of gene expressions, providing critical insights into gene regulation and disease mechanisms. However, the inherent challenges of high-dimensionality, noise, and sparsity in microarray data demand robust analytical approaches. Image processing techniques further enhance this analysis by extracting meaningful patterns from histological and microarray-derived visual data, aiding in biomarker discovery and classification. This study presents a novel framework leveraging deep neural networks for gene selection and cancer classification using microarray data, addressing the challenges of high dimensionality, noise, and sparsity. The proposed Gene-Optimized Neural Framework (GONF) integrates the Minimum Redundancy Maximum Relevance (mRMR) gene selection method with a deep Convolutional Neural Network (CNN) for effective feature selection and classification. By optimizing hyperparameters and employing advanced preprocessing techniques, the framework enhances computational efficiency and accuracy. Experiments were conducted on TCGA and AHBA datasets, utilizing metrics such as accuracy, precision and recall for evaluation. The GONF outperformed other methods, achieving a classification accuracy of 97% on the TCGA dataset and 95% on the AHBA dataset. The framework demonstrated significant reductions in false positive and false negative rates, improving cancer subtype predictions and providing biologically interpretable results. The findings highlight GONF's robustness and adaptability, paving the way for its application in other genomic studies and clinical settings.

The link of epithelial-mesenchymal transition (EMT) program with metastasis is well documented. However, the role of ROS in EMT process is self-contradictory. DpdtpA was a dithiocarbamate derivative (an iron chelator) that exhibits excellent growth and wound healing inhibitory effects in colorectal cancer (CRC) cell lines, but the underlying mechanism of action was not fully determined. The present data in this study revealed that the ROS derived from autophagic degradation of ferritin were conducive to EMT repression. Genetically knockdown of NCOA4 promoted expression of mesenchymal characteristics, supporting that NCOA4 involved EMT regulation. In addition, DpdtpA treatment also caused depletion of Gpx4 and xCT, triggering ferroptosis as Erastin acted. The causal relationship analysis demonstrated that depletion of Gpx4 and xCT, (or ferroptosis) contributed to the EMT inhibition. Moreover, there seemed to be a feedback loop between Gpx4 and xCT, knockdown of Gpx4 led to upregulation of xCT, but knockdown of xCT brought about downregulation of Gpx4. Further study demonstrated that the depletion of Gpx4 and xCT was due to enhanced autophagy. In addition, PI3K/AKT/mTOR/pathway was showed involving EMT and ferroptosis regulation. In short, our data suggested that the status of EMT and ferroptosis largely was dominated by the continuous NCOA4-mediated ROS production.

Background Neoadjuvant chemotherapy (NAC) is a standard approach for treating locally advanced gastric cancer (GC), but resistance in some patients can result in treatment toxicity and surgical delays without therapeutic benefit. Identifying biomarkers predictive of NAC response is crucial for personalized treatment strategies. This study evaluated circulating microRNAs (miRNAs) as potential biomarkers for NAC response. Materials and methods Plasma samples from 39 GC patients undergoing NAC followed by gastrectomy (NCT04223401) were collected before treatment. Four miRNAs (miR-19a, miR-21, miR-27a, miR-200c) were analyzed via quantitative real-time polymerase chain reaction. NAC response was assessed in histological specimens using the Becker tumor regression grade (TRG), which classifies patients as Responders (TRG 1-2) or Non-responders (TRG 3). Results Among 39 patients, 20 (51%) were Responders, and 19 (49%) were Non-responders. miR-19a, miR-21, and miR-200c were significantly upregulated in Non-responders (p < 0.05). ROC analysis revealed miR-19a (AUC: 0.693), miR-21 (AUC: 0.700), and miR-200c (AUC: 0.772) as predictive of resistance. Univariate analysis revealed a correlation between higher levels of miR-19a, miR-21, and miR-200c and a low neutrophil count, with increased resistance risk. Multivariate analysis confirmed miR-200c as an independent predictor of resistance (OR: 20.90; 95% CI: 1.54-283.73). Conclusions This pilot study identifies circulating miR-19a, miR-21, and miR-200c as novel biomarkers for poor NAC response in GC, providing a foundation for personalized treatment strategies.

Gallbladder cancer (GBC) is a highly aggressive malignancy with limited therapeutic options, particularly in underrepresented populations, including South Africa. Understanding the molecular landscape of GBC may provide novel insights into its pathogenesis and potential therapeutic targets. Molecular changes are known to be associated with GBC, however, there is a paucity of this information especially in African populations. Furthermore, within the tumour microenvironment, different immune cells contribute to GBC progression. We investigated gene expression patterns in GBC tumours and their association with different immune cells in a cohort of South African patients. RNA sequencing was conducted on 2 normal and 8 gallbladder cancer tissues from South African patients to identify differentially expressed genes. Bioinformatics tools were used for pathway analysis, while immune cell quantification was performed using the quanTIseq software and presented as median [IQR]. Verification studies were further carried out using real-time PCR on an independent cohort comprising 7 gallstone samples and 26 gallbladder tumour samples. A total of 65 genes were found to be significantly differentially expressed between the gallbladder tumours and gallstone controls. We also identified 37 upregulated and 28 downregulated genes in this cohort. Among the most upregulated genes, MUC16 was confirmed to be significantly overexpressed in tumours. Normal tissues exhibited a significantly higher proportion of dysregulated genes associated with B cells (17.132 [14.866-18.483], p < 0.0001) and M1 macrophages (18.943 [1.097-36.790], p < 0.0001) compared to tumours. In contrast, tumours showed a greater association with dysregulated genes linked to regulatory T cells (Tregs) (14.373 [9.696-20.162]) relative to normal tissues. Pathway analysis further revealed the upregulation of defective GALNT12, defective GALNT3, defective C1GALT1C1 and termination of O-glycan biosynthesis, highlighting key mechanisms potentially involved in tumour progression. The study has shown the dysregulation of key genes in South African gallbladder cancer patients. Specifically, MUC16 was verified to be significantly elevated in tumour samples. Furthermore, the association of these dysregulated genes with key immune cells in this patient group may further highlight their roles in dysfunctional immune processes linked with tumourigenesis.

Patients with metastatic testicular cancer (TC) treated with cisplatin-based chemotherapy (CBCT) are prone to develop metabolic syndrome (MetS). In an epigenome wide association study in patients with TC we have shown that DNA methylation was associated to CBCT. The aim of the study was to investigate whether there was a change in DNA methylation after treatment with CBCT, and if methylation status is related to the presence or development of MetS. In a prospective cohort of 67 TC patients who received CBCT, we assessed whole blood global methylation long interspersed nuclear element-1 (LINE-1) and DNA methylation at selected cytosine-phosphate-guanine dinucleotide (CpG) sites associated with MetS using targeted sequencing. Measured samples were taken before, one month after, and one year after CBCT. Development of MetS was assessed before and up to five years after CBCT. Serum platinum levels were measured to assess platinum exposure (PtAUC) within the first year after the start of CBCT. Data were used for paired comparisons, comparisons between groups, statistical modeling to account for covariates, and machine learning approaches to predict occurrence of MetS five years after diagnosis. Global methylation did not change during the first year after the start of CBCT (median 73.7% (25th -75th percentile 72.0-75.2) vs. 73.9% (72.5-75.1)). Seven out of the 16 other selected CpGs decreased. Patients with MetS before start of CBCT (N = 18) showed a larger decrease than patients without MetS (N = 49) for AC090023 (-11.6% vs. -8.2%, p = 0.008), NCAM2 (-6.5% vs. -1.6%, p = 0.030), and TOM1L2 (-5.8% vs. -2.6%, p = 0.003). The 15 patients who did not have MetS prior to CBCT, but developed MetS within five years after treatment showed an increase in global methylation (1.5% vs. - 0.6%, p = 0.008) after one year, and a decrease in TOM1L2 methylation (-4.0% vs. -1.6%, p = 0.015) when compared to patients who did not have prior to CBCT nor developed MetS (N = 34). There was no difference in PtAUC during the first year after the start of CBCT between the latter groups (70.0 vs. 67.9 days*mg/L, p = 0.206). Changes in global DNA methylation and TOM1L2 one year after the start of CBCT are associated with a higher risk for newly developing MetS within five years. This may indicate potential for tailored advice, based on epigenetic status, to patients treated with chemotherapy for TC to prevent development of MetS.