Search Results (803)

Objective: Obesity increases the risk of endometrial cancer (EC). In this study, we aimed to investigate the prognostic effect of sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, calculated with the help of cross-sectional imaging methods of muscle and visceral adipose tissue from body composition parameters, in EC. Methods: Patients diagnosed with EC were identified between January 2014 and June 2024. The combination of radiological markers and patient outcomes can predict prognosis. The skeletal muscle index (SMI) and visceral fat index (VFI) were calculated from computed tomography (CT) and/or abdominal magnetic resonance (MR) scans taken at the time of diagnosis at the Lumbal 3 (L3) vertebra level. The findings of these analyses demonstrate the strongest correlation with the ratio of muscle and visceral fat tissue throughout the body. The loss of muscle and fat is an unfavourable indicator in patients with EC. The present study analysed the prognostic values of sarcopenia, sarcopenic obesity, sarcopenic visceral obesity, and the visceral fat index in EC. The total skeletal muscle area was calculated in square centimetres. Body surface area (m²) was calculated using the Mosteller formula: ((height (cm) × weight (kg))/3600)^1/2. To normalize body composition components, the skeletal muscle index was calculated as cm²/m². Results: The study comprised a total of 236 EC patients. The prevalence of sarcopenia, sarcopenic obesity, and sarcopenic visceral obesity were found to be 48.31%, 33.47%, and 22.88%, respectively. The presence of sarcopenia, high VFI levels, sarcopenic obesity, and sarcopenic visceral obesity did not demonstrate statistical significance in the survival analysis. However, stage increase (p = 0.001), primary tumour localization in the lower uterine segment (p = 0.001), serous carcinoma (p = 0.001), increased grade in endometrioid carcinoma (p = 0.023), and lymphovascular invasion (p = 0.001) were significantly associated with increased mortality risk. The presence of sarcopenia was found to be significant in patients with obesity (p = 0.008) and those aged ≥ 65 years (p = 0.001). Conclusions: In EC survival, established prognostic factors such as serous histopathology, LVI positivity, and the extent of surgical staging are prioritised. The presence of these well-established markers means the potential effect of BMI-based observations, such as the ‘obesity paradox’, and even body composition measurements, such as sarcopenic obesity, are now statistically insignificant. Our findings suggest that aggressive tumour biology (serous type, LVI) and surgery, rather than metabolic variables such as sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, are the direct reason for the survival difference. This is due to the tumour’s aggressive nature and clinical characteristics (e.g., age at diagnosis, operability, stage, primary tumour localization in the lower uterine segment, serous carcinoma, grade, and LVI positivity) rather than metabolic variables. Full article

Background and Objective: Neuromodulators such as neuropeptide, neurotrophic factors and neurotransmitters are increasingly reported to be involved in glioblastoma (GBM) progression. Nonetheless, the association between neuromodulation-related genes (NMRGs) and GBM prognosis remains elusive. Hence, this study aims to identify clinically significant NMRGs that can form a prognostic gene signature for GBM patients. Methods and Results: Differential expression analysis of transcriptomic profiles extracted from GSE147352, GSE165595, TCGA and CGGA determined 272 differentially expressed NMRGs (deNMRGs) in GBM compared to normal brain tissue. The subsequent Kaplan–Meier survival analysis and Cox proportional hazard model further identified ten common deNMRGs (IGF2, RETN, EDNRB, C3AR1, CLCF1, NTRK1, OSMR, KCNN4, SLC18A3 and HTR7), forming a 10-NMRG signature. This signature stratifies GBM patients and consistently predicts poorer survival outcomes for the high-risk score group compared to the low-risk score group in the TCGA and CGGA cohorts. The gene set enrichment analysis and active-subnetwork-oriented enrichment analysis identified a connection between immunomodulation and tumour-associated hallmarks with the high-risk GBM patient group. Next, the correlation proportionality analysis identified a positive association between the signature genes with immune activators, immune suppressors and pro-motility genes. Additionally, high expressions of the 10-NMRGs were noted in the mesenchymal GBM subtype. Conclusions: Collectively, our analysis highlights the potential use of the 10-NMRG signature to stratify the high-risk GBM group with a strong association of immunomodulation and tumour-associated hallmarks that can contribute to the poor survival outcomes. Full article

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour that can metastasise early, may show resistance to systemic treatment, and has a poor prognosis. The use of tobacco products is closely related to the duration of their use, and approximately 95% of those diagnosed have a history of smoking. No satisfactory progress has been made in the prognosis with current treatment methods up to the present day. The treatment approach has traditionally involved long-term chemotherapy (CT) and radiotherapy (RT), and recent literature has focused on immunotherapy and genetic advancements. Surgery can only be performed in cases detected at an early stage. Although both chemotherapy and radiotherapy are indispensable options for most patients, their impact on prognosis and survival is limited. Although promising developments are expected in immunotherapy, its impact on survival is still very limited, lasting only about 2 months. In patients undergoing surgical resection as part of their treatment, overall survival (OS) ranges from 34 to 69 months. OS for 1 year is 84.8–93.8%, for 3 years is 60–71.2%, and for 5 years is 51.1–63.8%. The five-year survival rates are reported as follows: stage I 31–63.8%, stage II 25–65.5%, stage III 15–27.8%, and stage IV 0%. In this study, the prognosis and factors affecting prognosis in SCLC were investigated in light of current literature from a surgical perspective, and predictions were attempted to be made to lay the groundwork for personalised treatment approaches. Compared to non-small-cell lung cancer, the number of studies is quite limited. Most of the surgical case series were conducted in the past, retrospectively, and involved a small number of patients. Advances in immunotherapy are promising. In the early stages, resection and subsequent chemotherapy may be the main treatment. Full article

Background: Metastatic prostate cancers frequently harbour pathogenic aberrations in Homologous Recombination Repair (HRR) genes that confer sensitivity to PARP inhibitors (PARPi). Therefore, accurate identification of all eligible patients is needed. The development of a circulating tumour DNA (ctDNA) testing alternative is promising as genomic testing of archived tissue leads to a failure rate of up to 30–40% in prostate cancer. Methods: This was a bi-institutional retrospective cohort study of patients with metastatic prostate cancer treated at the Jewish General Hospital or the McGill University Health Center, Montreal, Canada, between 2021 and 2023. Molecular data and treatment information were abstracted from a chart review. Chi-square, Fisher’s exact test, and Mann–Whitney tests were used to assess differences between groups. Results: We identified 484 metastatic prostate cancer patients. Somatic and germline testing for HRR was performed in 55.4% (n = 268) and 20% (n = 97) patients, respectively. Somatic testing was performed on tissue (n = 192, 71.6%) or ctDNA from liquid biopsies (n = 18, 6.7%) or both (n = 58, 21.7%). Pathogenic somatic HRR alterations were detected in 48 patients (17.9%). BRCA2 was the most frequent (n = 17), followed by ATM (n = 11), then CHEK2 (n = 5). Amongst patients with germline testing, 13/97 (13.4%) had pathogenic alterations predicted to lead to deficient HRR, mostly BRCA2 (n = 9), and three had detectable BRCA2 in tissue. Dual testing modality (tissue+ctDNA) significantly enhanced the detection rate of HRR alterations 19/58 (32.7%) vs. 29/210 (13.8%) for single testing modality (tissue or ctDNA), p = 0.008. The rate of inconclusive results was significantly lower in dual testing modality 0/58 (0%) vs. 25/210 in single testing modality (11.9%), p = 0.003. Amongst the 14 patients who had discordant results between liquid and tissue tests, HRR abnormalities were more frequently identified in ctDNA (n = 11) vs. tissue (n = 3). Patients who had HRR deficiency detected only in ctDNA had older tissue samples (median 5.6 years) compared to those who had deficient HRR detected only in tissue (median 0.2 years; p = 0.14). Conclusions: These data highlight a potential role in implementing liquid biopsy—especially in patients who only have older archival tissue available or failed tissue testing—to improve the detection rate of deficient HRR. Our ongoing prospective study will further validate whether the addition of liquid biopsy can identify more patients who are eligible to receive precision therapies by increasing the rate of detection of HRR deficiency compared to routine tissue testing alone. Full article

Background/Objectives: Psychiatric morbidity is frequent in oncology, yet prevalence and correlates differ across tumour sites. Urogenital cancers, in particular, involve psychosocial stressors related to sexuality, fertility, continence, and body image, which may intensify anxiety and depression. This study aimed to estimate the proportion of psychiatric morbidity among psychiatry-assessed oncology inpatients in a real-world hospital setting to compare urogenital with non-urogenital malignancies and to examine clinical correlates and hospitalisation outcomes. Methods: We conducted a retrospective analysis of 174 oncology inpatients who were evaluated by liaison psychiatry and completed the Hospital Anxiety and Depression Scale (HADS) during admission to a tertiary hospital in Galați, Romania, between 2019 and 2022. All patients completed the Hospital Anxiety and Depression Scale (HADS) and underwent liaison psychiatry evaluation. Mixed anxiety–depressive disorder (ICD-10 F41.2) was the primary psychiatric outcome. Demographic, clinical, and functional data—including Eastern Cooperative Oncology Group (ECOG) performance status—were extracted from medical records. Comparative and multivariable analyses were performed to identify predictors of severe depressive symptoms (primary outcome, HADS-D ≥ 11) and to explore associations with length of stay and costs. Results: Overall, 59% of patients had elevated HADS-Anxiety and 62% elevated HADS-Depression, while 40% received a psychiatric diagnosis. Mixed anxiety–depressive disorder predominated, especially in cervical (95%), bladder (100%), and prostate (≈70–75%) cancers. Urogenital cancers showed significantly higher rates of anxiety/depression than non-urogenital cancers (85% vs. 46%, p < 0.01). Poorer ECOG status independently predicted severe depressive symptoms (OR 3.6, 95% CI 2.1–6.2, p < 0.001). Psychiatric morbidity was associated with a trend toward longer LOS (median 12 vs. 9 days, p ≈ 0.08) and ≈10% higher hospital costs. Conclusions: Anxiety and depression were highly frequent among psychiatry-assessed oncology inpatients, particularly in urogenital malignancies. Functional impairment strongly correlates with psychiatric morbidity. These findings underscore the need for systematic screening and risk-stratified psycho-oncologic interventions to improve patient outcomes and resource utilisation. Full article

Radiomics has emerged as a promising tool for non-invasive tumour phenotyping in breast cancer, providing valuable insights into tumour heterogeneity, response prediction, and risk stratification. However, traditional radiomic approaches often rely on correlative patterns of image analysis to clinical data and lack direct biological interpretability. Combining information provided by radiomics with genomics or other multi-omics data can be important to personalise diagnostic and therapeutic work up in breast cancer management. This review aims to explore the current progress in integrating radiomics with multi-omics data—genomics and transcriptomics—to establish biologically grounded, multidimensional models for precision management of breast cancer. We will review recent advances in integrative radiomics and radiogenomics, highlight the synergy between imaging and molecular profiling, and discuss emerging machine learning methodologies that facilitate the integration of high-dimensional data. Applications of radiogenomics, including breast cancer subtype and molecular mutation prediction, radiogenomic mapping of the tumour immune microenvironment, and response forecasting to immunotherapy and targeted therapies, as well as lymph nodes involvement, will be evaluated. Challenges in technical limitations including imaging modalities harmonization, interpretability, and advancing machine learning methodologies will be addressed. This review positions integrative radiogenomics as a driving force for next-generation breast cancer care. Full article

Mercury exposure has been linked to male infertility. Given that mercury chloride (HgCl₂) may promote an oxido-inflammatory milieu associated with pathophysiological derangements, it is hypothesised that Thymoquinone (TQ), an antioxidant and anti-inflammatory agent, may mitigate the gradual harmful effects of mercury exposure on rat testes, epididymis, and hypothalamus, as these organs are vital to reproductive function. To test this hypothesis, 40 rats (strain: Wistar; sex: male) were randomly assigned to five cohorts of eight rats each. After a 7-day acclimation, treatments were dispensed for 28 consecutive days accordingly: Cohort I: distilled water only, as control; Cohort II: HgCl₂ only (20 µg/mL); Cohort III: TQ only (2.5 mg/kg); Cohort IV: HgCl₂ + TQ (20 µg/mL + 2.5 mg/kg); and Cohort V: HgCl₂ + TQ (20 µg/mL + 5 mg/kg). Co-treatment with TQ preserved the body and organ weight of the HgCl₂ exposed animals. However, TQ did not reduce HgCl₂-induced dysfunction in sperm function and morphology. The serum follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone were increased significantly (p < 0.05) by TQ co-treatment, while decreasing the prolactin level. TQ administration also increased (p < 0.05) testicular enzymes, including alkaline phosphatase (ALP), lactate dehydrogenase (LDH), acid phosphatase (ACP), and glucose-6-phosphate dehydrogenase (G6PD) activities, which HgCl₂ decreased. TQ administration increased (p < 0.05) HgCl₂-induced decreases in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), glutathione-s-transferase (GST), and total sulfhydryl group (TSH) levels in the testes, epididymis, and hypothalamus of experimental rats. Further, TQ reduced HgCl₂-mediated increases in RONS-reactive oxygen and nitrogen species; LPO–lipid peroxidation; PC–protein carbonyl formation; and XO–xanthine oxidase activity. Furthermore, levels of inflammatory biomarkers, including tumour necrosis factor alpha (TNF-α), nitric oxide (NO), interleukin-1 beta (IL-1β), and myeloperoxidase (MPO), were decreased (p < 0.05) in the co-treated groups, with a higher dose of TQ (5.0 mg/kg) showing a more pronounced protective effect. Additionally, TQ co-administration increased Bax and decreased Bcl-2 and p53 protein levels (p < 0.05), thereby protecting the rats’ testes, epididymis, and hypothalamus from HgCl₂-induced apoptosis. Molecular docking simulation analysis revealed TQ interaction dynamics with PPAR-α and PPAR-δ to suppress NF-kB-mediated pro-inflammatory sequela as well as activate Nrf-2-mediated antioxidant defence system. These predicted biological effects of TQ resonate with the findings from the in vivo studies. Therefore, supplementation with TQ may help reduce chemical-induced toxicities, including HgCl₂‘s reproductive toxicity. Full article

Classifying brain tumour transcriptomic data is crucial for precision medicine but remains challenging due to high dimensionality and limited interpretability of conventional models. This study benchmarks three image-based deep learning approaches, DeepInsight, Fotomics, and a novel saliency-guided convolutional neural network (CNN), for transcriptomic classification. DeepInsight utilises dimensionality reduction to spatially arrange gene features, while Fotomics applies Fourier transforms to encode expression patterns into structured images. The proposed method transforms each single-cell gene expression profile into an RGB image using PCA, UMAP, or t-SNE, enabling CNNs such as ResNet to learn spatially organised molecular features. Gradient-based saliency maps are employed to highlight gene regions most influential in model predictions. Evaluation is conducted on two biologically and technologically different datasets: single-cell RNA-seq from glioblastoma GSM3828672 and bulk microarray data from medulloblastoma GSE85217. Outcomes demonstrate that image-based deep learning methods, particularly those incorporating saliency guidance, provide a robust and interpretable framework for uncovering biologically meaningful patterns in complex high-dimensional omics data. For instance, ResNet-18 achieved the highest accuracy of 97.25% on the GSE85217 dataset and 91.02% on GSM3828672, respectively, outperforming other baseline models across multiple metrics. Full article

As a traditional Chinese medicinal herb, Centipeda minima (L.) A. Braun & Asch is known for its effects in dispersing wind-cold, clearing nasal passages, and relieving coughs. Current research has identified various chemical constituents isolated from C. minima, including volatile oils, flavonoids, organic acids, and terpenoids. These compounds demonstrate multiple pharmacological activities such as anti-inflammatory, antioxidant, anti-allergic, and anti-tumour effects. This review summarizes the chemical constituents, pharmacological effects, and clinical applications of C. minima. Furthermore, based on the concept of Quality Markers (Q-Markers) in Chinese medicine, potential Q-Markers for C. minima are predicted and analyzed from five perspectives: botanical phylogeny, specificity of chemical composition, measurability of constituents, traditional efficacy, and medicinal properties. Compounds including brevilin A, arnicolide C, arnicolide D, and helenalin are proposed as candidate Q-Markers for C. minima, providing a scientific basis for elucidating its pharmacologically active substances and establishing quality evaluation criteria. Full article

Objectives: This study aimed to investigate the diagnostic performance of imaging-based biomarkers from computed tomography (CT) and magnetic resonance imaging (MRI) for prediction of malignant and borderline malignant ovarian tumours. Methods: 195 consecutive patients with suspected primary epithelial ovarian cancer were included from the retrospective “Prognostic and Diagnostic Added Value of Medical Imaging in Staging and Treatment Planning of Gynaecological Cancer” (PRODIGYN) study. The radiological stage, according to the International Federation of Gynaecology and Obstetrics system (rFIGO), magnetic resonance imaging (MRI)-based Ovarian-Adnexal Reporting and Data System (O-RADS-MRI) score, and the mean apparent diffusion coefficient (ADC_mean) were investigated for prediction of ovarian malignancy, with histopathology as reference. The same imaging biomarkers were applied to the borderline tumour cohort (n = 33) to predict malignant/adverse features, such as micro-invasion. Results: The rFIGO stage demonstrated high accuracy for ovarian malignancy, with an area under the curve (AUC) of 0.98 (95% confidence interval (CI) = 0.97–0.99). On lesion level, the sensitivity and specificity of the O-RADS-MRI score to predict ovarian malignancy, after adjusting for correlated data structure, was 1 (CI: 0.96–1) and 0.82 (CI: 0.70–0.90), respectively. The performance of ADC_mean to predict ovarian malignancy on lesion level was moderately high, with AUC = 0.78 (95% CI 0.68, 0.88). Discrimination of adverse features in borderline tumours was not improved. Conclusions: rFIGO and O-RADS-MRI showed excellent performance and outperformed ADC_mean as predictive tools for ovarian malignancy but could not predict adverse features in borderline tumours. Full article

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article

Background/Objectives: Gliomas are the most common tumours of the central nervous system (CNS), classified into grades I to IV based on their malignancy. Genetic and epigenetic alterations play a crucial role in glioma progression. DNA methyltransferases (DNMTs) are vital enzymes responsible for DNA methylation, with DNMT1 and DNMT3 catalysing the addition of a methyl group to the 5-carbon of cytosine in CpG dinucleotides. Targeting DNMTs with DNA methyltransferase inhibitors (DNMTi) has become a promising therapeutic approach in tumour treatment. In this study, in silico screening tools were employed to evaluate potential inhibitors of DNMT1, DNMT3A, and DNMT3B for the treatment of glioblastoma multiforme (GBM). Methods: The Gene2Drug platform was used to screen compounds and rank them based on their capacity to dysregulate DNMT genes. PRISM viability assays were performed on 68 cell lines, and DepMap data were analyzed to assess the antitumor activities of these compounds and their target genes. Candidate drug similarity was evaluated using DSEA, and compounds with p < 1 × 10⁻³ were considered statistically significant. Gene-compound interactions for DNMT1, DNMT3A, and DNMT3B were confirmed using Expression Public 24Q2, while Prism Repositioning Public data were analyzed via DepMap. Results: Glioblastoma cell lines showed sensitivity to compounds including droperidol, demeclocycline, benzthiazide, ozagrel, pizotifen, tracazolate, norcyclobenzaprine, monocrotaline, dydrogesterone, 6-benzylaminopurine, and nifedipine. SwissTargetPrediction was utilised to identify alternative molecular targets for selected compounds, revealing high-probability matches for droperidol, pizotifen, tracazolate, monocrotaline, dydrogesterone, and nifedipine. Conclusions: Integrating computational approaches with biological insights and conducting tissue-specific and experimental validations may significantly enhance the development of DNMT-targeted therapies for gliomas. Full article

Background/Objectives: Testicular germ cell tumours (GCT) have high cure rates, especially in early stages. MicroRNA-371a-3p (M371) has recently emerged as a highly sensitive biomarker for malignant GCTs, except teratoma. This study aimed to evaluate the diagnostic performance of M371-test in a real-life clinical setting, compared to conventional markers alpha-fetoprotein (AFP), lactate-dehydrogenase (LDH), and beta-human chorionic gonadotropin (β-HCG) in patients with suspected GCT. Methods: The study, approved by the Ethic-Committee of the Provincial Hospital of Bolzano (N.97-2021), included 91 M371-tests, performed from March 2021 to May 2025. A total of 75 patients had suspected GCT; 19 healthy males served as control. Serum levels of M371, AFP, LDH, and β-HCG were compared with final histopathological diagnosis. M371 was also assessed in controls to evaluate test performance. Secondary analyses investigated correlations between preoperative M371 levels and tumour size in non-metastatic patients, and between M371-levels and clinical stage in the entire GCT cohort. A cut-off of RQ > 5 (relative quantification) was used to calculate sensitivity, specificity, and predictive values. Results: M371 showed a sensitivity of 90.9% and specificity of 89.3%, outperforming in terms of sensitivity AFP (20.4%/96.4%), LDH (40.9%/96.4%), and β-HCG (43.1%/100%). Positive predictive value (PPV) and negative predictive value (NPV) were 93.0% and 86.2%, respectively. Sensitivity was 95% for non-seminomas and 87.5% for seminomas. In non-metastatic patients, M371 levels correlated with tumour size and were significantly higher in advanced stages (median RQ 1128.35 vs. 98.36; p = 0.015). Conclusions: M371 showed excellent diagnostic performance, even for small tumours, supporting its clinical use. Further studies are needed to define its role in treatment planning and follow-up. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC. Full article