Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “molecular stratification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2004

Perspectives and limitations of gene expression profiling in rheumatology: new molecular strategies.

The deciphering of the sequence of the human genome has raised the expectation of unravelling the specific role of each gene in physiology and pathology. High-throughput technologies for gene expression profiling provide the first practical basis for applying this information. In rheumatology, with its many diseases of unknown pathogenesis and puzzling inflammatory aspects, these advances appear to promise a significant advance towards the identification of leading mechanisms of pathology. Expression patterns reflect the complexity of the molecular processes and are expected to provide the molecular basis for specific diagnosis, therapeutic stratification, long-term monitoring and prognostic evaluation. Identification of the molecular networks will help in the discovery of appropriate drug targets, and permit focusing on the most effective and least toxic compounds. Current limitations in screening technologies, experimental strategies and bioinformatic interpretation will shortly be overcome by the rapid development in this field. However, gene expression profiling, by its nature, will not provide biochemical information on functional activities of proteins and might only in part reflect underlying genetic dysfunction. Genomic and proteomic technologies will therefore be complementary in their scientific and clinical application.

Animals↗
PubMed2005

Molecular imaging. A new approach to nuclear cardiology.

Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk stratification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentation will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutic angiogenesis.

Animals↗
PubMed2026

Integrated Clinicopathologic and Multiomic Profiling Reveals MEIS1-Rearranged Sarcoma as a Distinct Entity With 2 Prognostic Subgroups.

Sarcomas with MEIS1 fusions represent a rare, recently recognized group of mesenchymal neoplasms with a predilection for genitourinary and gynecologic sites. A subset exhibits skeletal muscle differentiation resembling spindle cell rhabdomyosarcoma. Existing literature is limited to case reports and small series, with scant comprehensive clinicopathologic, molecular, and outcome data. In this study, we analyzed a multi-institutional cohort of 20 MEIS1-rearranged sarcomas using integrated clinicopathologic review, genomic profiling, and DNA methylation analysis. The tumors occurred in 17 females and 3 males (median age, 41 years; range, 6-58 years), arising mainly in the uterus/vagina (n = 12), vulva/perineum (n = 4), bone (n = 2), and kidney (n = 2), with a median size of 9 cm (range, 2.5-20 cm). Histology showed mostly bland spindle cells in fascicles/storiform patterns, alternating cellularity, fibromyxoid stroma, prominent vascularity, and adipose metaplasia (45%). A subset of cases featured high-grade morphology with epithelioid cells and increased mitotic activity. Skeletal muscle markers were variably positive in 9 cases. Fusions involved MEIS1 with NCOA2 (16/20), NCOA1 (3/20), or FOXO1 (1/20). Recurrent additional genomic alterations included CTNNB1 mutations (31.6%) and MDM2 amplification (15%). DNA methylation profiling showed that MEIS1-rearranged sarcomas formed a unifying cluster comprising 2 subgroups, regardless of rhabdomyosarcomatous phenotype, clearly separated from other mesenchymal neoplasms, including various rhabdomyosarcoma subtypes and uterine sarcomas. The 2 DNA methylation (Meth) subgroups correlated with differences in genome-wide copy number variation (CNV) status (Meth-CNV high vs Meth-CNV low), with Meth-CNV high tumors characterized by high mitotic rate, frequent tumor necrosis, recurrent co-occurring CTNNB1 and MDM2 alterations, and recurrent chromosomal arm-level changes. Most importantly, this subgroup exhibited significantly worse overall survival (P = .027) and disease-free survival (median, 5 vs 99 months; P = .017). This study establishes MEIS1-rearranged sarcoma as a distinct entity with generally indolent but potentially aggressive behavior. The 2 methylation/CNV subgroups provide potential utility for prognostic stratification and highlight actionable molecular targets in high-risk cases.

Humans↗
PubMed2005

Comparison of marine copepod outfluxes: nature, rate, fate and role in the carbon and nitrogen cycles.

We compare the nature of copepod outfluxes of nonliving matter, the factors controlling their rate and their fate, and finally their role, particularly their relative importance in the carbon and nitrogen cycle. Copepods release dissolved matter through excretion and respiration and particulate matter through production of faecal pellets, carcasses, moults, and dead eggs. Excretion liberates several organic C, N, and P compounds and inorganic N and P compounds, with inorganic compounds constituting the larger part. The faecal pellets of copepods are covered by a peritrophic membrane and have a highly variable size and content. There is less information on the nature of other copepod particulate products. The weight-specific rates of posthatch mortality, respiration, excretion, and faecal pellet production have similar C or N levels and are higher than those of moulting and egg mortality. In general, most important factors controlling these rates are temperature, body mass, food concentration, food quality, and faunistic composition. Physical and biological factors govern the vertical fate of copepod products by affecting their sedimentation speed and concentration gradient. The physical factors are sinking speed, advection, stratification, turbulent diffusion, and molecular diffusion. They influence the sedimentation speed and degradation of the copepod products. The biological factors are production, biodegradation (by zooplankton, nekton, and microorganisms) and vertical migration of copepods (diel or seasonal). Physical degradation and biodegradation by zooplankton and nekton are faster than biodegradation by microorganisms. The most important copepod outfluxes are excretion and faecal pellet production. Excretion offers inorganic nutrients that can be directly used by primary producers. Faecal pellets have a more important role in the vertical transport of elements than the other particulate products. Most investigation has focused on carbon burial in the form of copepod faecal pellets, measured by sediment traps, and on the role of ammonia excretion in nutrient recycling. Full evaluation of the role of copepod products in the transport and recycling of elements and compounds requires a quantification of all copepod products and their different fates, particularly detritiphagy, remineralization, and integration as marine snow.

Animals↗
PubMed2001

Infectious complications of febrile leukopenia.

It can be foreseen that in the years to come major improvements in neutropenic host infections will be achieved regarding the exact identification of risk factors, allowing better patient stratification; the application of molecular techniques to recognize pathogens; the development of effective new oral antimicrobials allowing home therapy or abbreviated hospitalization; the development of new antifungals; and the development of new effective immunomodulators and cytokines to ameliorate chemotherapy-induced neutropenia. In the years to come the threat of nosocomial infections unfortunately will not be eliminated, while the development of major new parenteral antibiotics cannot be foreseen. It is therefore the caregiver/physician himself who, by applying rational antibiotic policies and strict handwashing rules, will probably escape, for his neutropenic patient's sake, the imminent threat of multiresistant pathogens.

Anti-Infective Agents↗
PubMed2004

[Gastric MALT lymphoma and gastrointestinal stromal tumors (GIST)].

Gastric lymphoma and gastrointestinal stromal tumours (GISTs) are rare malignancies of the upper gastrointestinal tract. The most common gastric lymphoma are low-grade marginal zone B-cell lymphoma (MZBCL) of MALT type. They develop as a consequence of chronic Helicobacter pylori infection, the histological hallmark are lymphoepithelial lesions. In early stages of disease, H. pylori eradication alone may lead to complete lymphoma remission in up to 75% of cases. Nonresponder or locally advanced lymphoma should be treated with radiation therapy. Advanced lymphoma may be treated with the nucleoside analogon cladribine within clinical trials. Based on clinical and novel molecular markers a risk stratification and a prediction of response to therapy might be possible in the future. GISTs are mesenchymal tumours that characteristically express CD-117 (c-kit). They are mostly localized in the upper gastrointestinal tract and are frequently diagnosed in an advanced stage. Conventional chemotherapy is ineffective. For resectable non-metastasized tumours surgical therapy is the treatment of choice. Imatinib is the first and so far only effective systemic therapy which is presently indicated in irresectable or metastasized GISTs. More than 80% of patients respond to imatinib therapy either with partial remission or stable disease. FDG-PET plays an important role in the early prediction of response to imatinib therapy. The optimal dosage and duration of treatment and the role of imatinib as adjuvant or neo-adjuvant therapy for GISTs remains to be defined.

Gastric Mucosa↗
PubMed2002

Controversies and advances in the management of Wilms' tumour.

Wilms tumour is one of the success stories of paediatric oncology with long term survival approaching 90% in localised disease and over 70% for metastatic disease. Although appearing relatively simple compared to other cancer treatment regimens, successful treatment of Wilms tumour requires meticulous attention to correct staging of the tumour and good communication between the paediatric surgeon, pathologist and oncologist. The controversy of whether pre-operative chemotherapy results in a reduced overall burden of treatment compared to immediate nephrectomy has been addressed by the recently closed UKW3 randomised trial. Challenges remain in identification of histological and molecular risk factors for stratification of treatment intensity to allow safe reduction in therapy and avoidance of late sequelae for the majority while leading to increased biological insights and ultimately novel therapies for the minority of high risk tumours. Genetic predisposition to Wilms tumour is conferred by several genes, some of which cause malformation rather than cancer and may be of low penetrance. The proportion of children with heritable disease is uncertain and there remains a need to collect data on the need for screening in this susceptible population.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Molecular classification of breast cancer: limitations and potential.

Reverse transcription polymerase chain reaction and DNA microarrays are increasingly used in the clinic and in clinical research as prognostic or predictive tests. Results from these tests led to novel risk stratification methods and to new molecular classification of breast cancer. Some of these tools already complement existing diagnostic tests and can aid medical decision making in some situations. Better understanding of the molecular classes of breast cancer, independent of their prognostic and predictive values, may also lead to new biological insights and eventually to better therapies that are directed toward particular molecular subsets. However, there is substantially less experience with these emerging technologies than with the more established methods, the accuracy of which is often overestimated. This review discusses some of the limitations and strengths of current gene expression-based molecular classification of breast cancer. To provide context for this discussion, we also briefly examine the performance of estrogen receptor immunohistochemistry, which represents an essential part of the routine diagnostic workup for all breast cancer patients.

Biomarkers, Tumor↗
PubMed2026

Deep learning-based cross-attention fusion of multimodal MRI for survival prediction and risk stratification in IDH-wildtype glioblastoma: a multicenter study.

BACKGROUND: Glioblastoma (GBM) exhibits profound molecular and spatial heterogeneity, complicating prognostic evaluations. While multiparametric MRI provides crucial multidimensional biological information, conventional end-to-end deep learning integration strategies, such as early or late fusion, often fail to capture complex nonlinear cross-modal interactions. We aimed to systematically evaluate a cross-attention fusion (CAF) architecture for GBM survival prediction and quantify its incremental prognostic value relative to existing clinical tools. METHODS: In this multicenter retrospective study, 386 adults with IDH-wildtype, WHO grade 4 GBM were assembled from an institutional cohort (n = 226), the Chinese Glioma Genome Atlas (CGGA, n = 62), and The Cancer Genome Atlas (TCGA, n = 98). Using a unified 3D ResNet-18 backbone, we compared single-modality models, early fusion, late fusion, and CAF on preoperative T1-weighted, contrast-enhanced T1-weighted (T1CE), and T2-weighted MRI, and integrated the resulting deep learning risk score with routine clinical variables through multivariable Cox regression. Performance was assessed using Harrell's C-index, time-dependent AUC, and decision curve analysis. RESULTS: CAF showed numerically higher, more consistent C-index trends than early fusion, late fusion, and single-modality models (pooled C-index 0.629, 95% CI 0.594-0.664), although pairwise differences in time-dependent AUC were not statistically significant. Integrating clinical variables raised the pooled C-index to 0.691 (95% CI 0.660-0.721) in the treatment-era model, with comparable performance across the three cohorts (Local 0.688; CGGA 0.716; TCGA 0.689); a pre-treatment configuration excluding adjuvant therapy yielded a pooled C-index of 0.642. Under leave-one-cohort-out external validation, the combined model retained significant risk stratification in all held-out cohorts (C-index 0.63-0.71; all log-rank P&#xa0;<&#xa0;0.01), albeit with attenuated discrimination. The deep learning risk score remained independent after multivariable adjustment (HR 1.41 per SD, 95% CI 1.26-1.57; P&#xa0;<&#xa0;0.001). Kaplan-Meier analysis confirmed significant high- versus low-risk separation in all cohorts, and decision curve analysis showed greater net benefit than clinical-only and deep-learning-only models. CONCLUSION: The CAF-derived risk score offers prognostic information complementary to routine clinical variables, representing a promising noninvasive tool for individualized risk stratification when molecular profiling is incomplete or unavailable; these findings warrant prospective external validation before clinical use.

cross-attention fusion↗
PubMed2003

The molecular biology of Euglena gracilis. XV. Recovery from centrifugation-induced stratification.

The contents of Euglena gracilis cells can be separated in vivo by ultracentrifugation. Within the unbroken cell, each set of components forms a distinct layer according to their respective densities. The degree of segregation increases with both the g-force and the time of centrifugation, up to a maximum at 100,000 x g for 1 h, when six distinct strata can be observed. When returned to normal growth conditions, essentially all the cells return to the normal state and growth pattern. Greater g-forces or longer exposures do not alter the observable strata, but the ability of the cells to recover is diminished. Smaller g-forces result in less separation of cellular contents and all cells recover, even after 18 h of exposure. Euglena cells stratified at 100,000 x g for 1 h were returned to normal growth conditions; recovery was followed microscopically and by the rate of utilization of oxygen as well as that of the single carbon source. The cells recovered their normal state within 1 to 2 h, which is only a tenth of the normal doubling time. The mechanism for this recovery involves a natural process of change in cell shape caused by contraction and relaxation of the pellicle, a cell surface structure.

Animals↗
PubMed2026

Proteomics as a theranostic compass in BCR::ABL1-negative myeloproliferative neoplasms: Integrating biomarker discovery with therapeutic stratification.

Classic BCR::ABL1-negative myeloproliferative neoplasms (MPNs)-polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis-are clonal haematopoietic stem cell disorders with marked heterogeneity in clinical phenotype, disease trajectory, and therapeutic response. Genomic stratification by driver and cooperating mutations only partially accounts for this variability, leaving gaps in predicting thrombotic risk, fibrotic progression, leukaemic transformation, and treatment benefit. Proteomics bridges this gap by providing function-proximal readouts of protein abundance, post-translational modifications, pathway activity, and intercellular signalling that genomics and transcriptomics cannot capture, positioning it as a theranostic platform in which the same molecular readouts simultaneously inform diagnostic stratification and therapeutic decision-making. We propose a five-stage translational framework spanning from discovery-scale mass spectrometry and affinity-based plasma profiling to targeted validation, multicentre standardisation, and machine learning-integrated clinical panels. Proteomic evidence is synthesised across the following four disease axes: clonal fitness in haematopoietic stem and progenitor cells; bone marrow microenvironmental remodelling and fibrosis; chronic inflammation and thrombosis; and leukaemic transformation. We further describe how phosphoproteomics reveals resistance mechanisms to JAK inhibitors, including AXL-MAPK bypass and PP2A-autophagy-mediated tolerance, and how protein-level biomarkers (BCL2-BCL-XL, RAS-ERK, CAMK2G, and ROCK1/2) can guide individualised therapeutic selection. Affinity-based platforms (Olink PEA and SomaScan) and spatially resolved technologies (CODEX and single-cell proteomics) complement discovery proteomics. At present, however, this evidence base is constrained by small and heterogeneous cohorts, limited cross-platform reproducibility, and a scarcity of independent external validation for candidate protein panels. Realising this vision will require multicentre standardisation, analytically validated panel assays, and prospective clinical studies that translate molecular findings into decision-grade tools for patients with MPNs.

Humans↗
PubMed2026

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans↗
PubMed2006

Medulloblastomas: new directions in risk stratification.

Medulloblastomas (MBs) are the most common malignant brain tumors in children. Current therapeutic approaches combine surgery, radiotherapy, and chemotherapy. Although, there has been significant improvement in long-term survival rates, the tumor remains incurable in about a third of patients while cognitive deficits and other sequelae of therapy are common among long-term survivors. Hence a major challenge remains to differentiate high-from low-risk patients and to tailor therapy based on the degree of biological aggressiveness. A clinical risk-stratification system has been widely used in MBs based on age, extent of resection and the Chang staging system. However, recent reports indicate that these clinical variables are inadequate methods of defining disease risk. This has prompted search for new markers for MB stratification. Recent studies indicate that the classification of MBs according to profiles of histopathology and molecular abnormalities possibly help better risk-stratification of patients, thereby rationalizing approaches to therapy, increasing cure rate, reducing long-term side effects and developing novel therapeutic strategies. The most accurate outcome prediction till date has been obtained through microarray gene expression profiling. In this article, the current histopathological classification and the recent advances in molecular genetics of MBs are reviewed. Global efforts to translate this knowledge of disease biology into clinical practice especially as outcome predictors are highlighted.

Brain Stem Neoplasms↗
PubMed2000

Primate DAX1, SRY, and SOX9: evolutionary stratification of sex-determination pathway.

The molecular evolution of DAX1, SRY, and SOX9, genes involved in mammalian sex determination, was examined in six primate species. DAX1 and SRY have been added to the X and Y chromosomes, respectively, during mammalian evolution, whereas SOX9 remains autosomal. We determined the genomic sequences of DAX1, SRY, and SOX9 in all six species, and calculated K(a), the number of nonsynonymous substitutions per nonsynonymous site, and compared this with the K(s), the number of synonymous substitutions per synonymous site. Phylogenetic trees were constructed by means of the DAX1, SRY, and SOX9 coding sequences, and phylogenetic analysis was performed using maximum likelihood. Overall measures of gene and protein similarity were closer for DAX1 and SOX9, but DAX1 exhibited nonsynonymous amino acid substitutions at an accelerated frequency relative to synonymous changes, similar to SRY and significantly higher than SOX9. We conclude that, at the protein level, DAX1 and SRY are under less selective pressure to remain conserved than SOX9, and, therefore, diverge more across species than does SOX9. These results are consistent with evolutionary stratification of the mammalian sex determination pathway, analogous to that for sex chromosomes.

Amino Acid Sequence↗
PubMed2005

stam--a Bioconductor compliant R package for structured analysis of microarray data.

BACKGROUND: Genome wide microarray studies have the potential to unveil novel disease entities. Clinically homogeneous groups of patients can have diverse gene expression profiles. The definition of novel subclasses based on gene expression is a difficult problem not addressed systematically by currently available software tools. RESULTS: We present a computational tool for semi-supervised molecular disease entity detection. It automatically discovers molecular heterogeneities in phenotypically defined disease entities and suggests alternative molecular sub-entities of clinical phenotypes. This is done using both gene expression data and functional gene annotations. We provide stam, a Bioconductor compliant software package for the statistical programming environment R. We demonstrate that our tool detects gene expression patterns, which are characteristic for only a subset of patients from an established disease entity. We call such expression patterns molecular symptoms. Furthermore, stam finds novel sub-group stratifications of patients according to the absence or presence of molecular symptoms. CONCLUSION: Our software is easy to install and can be applied to a wide range of datasets. It provides the potential to reveal so far indistinguishable patient sub-groups of clinical relevance.

Calibration↗
PubMed2005

Molecular imaging in the clinical arena.

Molecular imaging is an emerging field that aims to integrate patient-specific and disease-specific molecular information with traditional anatomical imaging readouts. The information provided by this field may ultimately allow for noninvasive or minimally invasive molecular diagnostic capabilities, better clinical risk stratification, more optimal selection of disease therapy, and improved assessment of treatment efficacy. In this update, we first provide an overview of clinically relevant molecular imaging technologies and imaging agents. Next, their applications to disease detection, drug discovery, and biomedical research are discussed. To specifically demonstrate the potential of molecular imaging, we highlight recent advances in clinical and preclinical molecular imaging of cancer and atherosclerosis.

Biotechnology↗
PubMed2006

Molecular prognostic markers in resectable colorectal liver metastases: a systematic review.

BACKGROUND: Determination of prognosis in patients with resectable colorectal liver metastases (CLM) is desirable in order to improve case selection for surgery and tailor adjuvant treatment according to individual recurrence risk. Conventional clinicopathological factors lack the sensitivity to accurately achieve this goal. Consideration of tumour biology and the identification of molecular prognostic markers may allow more accurate risk stratification. METHOD: This systematic review examines evidence from published manuscripts looking at molecular markers in resectable colorectal liver metastases and their correlation with disease recurrence and survival following hepatectomy. RESULTS: Studies have yielded promising results in the search for prognostic molecular markers of CLM. Molecular biomarkers from varied aspects of tumour biology have been examined and a number of these, including proliferation indices, telomerase, thymidylate synthase, microvessel density and thrombospondin-1 appear to have prognostic utility in this context. Validation of other markers, notably p53, has been limited by a failure of methodologies to account for their biological complexity. CONCLUSIONS: A biomarker-based approach may yield significant benefits through informed treatment of resectable metastatic colorectal malignancy. Standardised retrospective analyses are necessary to confirm preliminary findings and identify existing and novel markers for inclusion into prospective studies. Assessment and verification of multiple molecular markers in this manner may allow molecular profiling of metastases and tailoring of therapy according to the biological aggressiveness of individual tumours. The advent of genomic- and proteomic-based technologies will allow the simultaneous analysis of multiple molecular markers and the derivation of disease profiles associated with disease recurrence and poor survival.

Apoptosis↗
PubMed2025

Development and validation of a novel risk stratification signature derived from migrasome and tumor microenvironment-related genes for molecular subtyping and improving clinical outcomes in head and neck squamous cell carcinoma.

BACKGROUND: The tumor microenvironment (TME) and migrasomes released by tumor cells significantly influence carcinogenesis and immune evasion. However, our understanding of the prognostic and therapeutic implications of migrasome and tumor microenvironment-related genes (mtmRGs) in head and neck squamous cell carcinoma (HNSCC) remains limited. METHODS: We explored the relationship between mtmRGs and HNSCC prognosis by utilizing The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Subsequently, we developed an innovative prognostic signature, and assessed its prognostic significance using the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and Cox regression analyses. To explore the underlying mechanisms, we conducted gene set variation analysis (GSVA), gene set enrichment analysis (GESA), and immune infiltration analysis. A nomogram was developed to estimate the overall survival (OS) rates for HNSCC patients. Lastly, we chose P4HA1, which was part of the signature, for additional experimental validation in vitro and in vivo. RESULTS: The mtmRGs signature effectively classifies HNSCC patients into two distinct risk subgroups, with the high-risk cohort demonstrating significantly poorer OS. The risk score serves as an independent prognostic factor for HNSCC patients; those with lower risk scores are more likely to exhibit favorable responses to immunotherapy, particularly with CTLA4 inhibitors. Furthermore, a lower risk score is significantly correlated with the sensitivity of HNSCC patients to cyclophosphamide, gemcitabine, and axitinib. CONCLUSION: This study presents an innovative gene signature associated with mtmRGs, which may be utilized both for predicting survival and directing personalized chemotherapy and immunotherapy regiments for patients with HNSCC.

Humans↗