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OBJECTIVE: To assess the prediction accuracy of recent optical and numerical models for the spectral reflectance and color of monolithic samples of dental materials with different thicknesses. METHODS: Samples of dental resin composites of Aura Easy Flow (Ae1, Ae3 and Ae4 shades) and Estelite Universal Flow Super Low (A1, A2, A3, A3.5, A4 and A5 shades) with thicknesses between 0.3 and 1.8 mm, as well as Estelite Universal Flow Medium (A2, A3, OA2 and OA3 shades) with thicknesses between 0.4 and 2.0 mm, were used. Spectral reflectance and transmittance factors of all samples were measured using a X-Rite Color i7 spectrophotometer. Four analytical optical models (2 two-flux models and 2 four-flux models) and two numerical models (PCA-based and L*a*b*-based) were implemented to predict spectral reflectance of all samples and then convert them into CIE-L*a*b* color coordinates (D65 illuminant, 2°Observer). The CIEDE2000 total color difference formula (ΔE00) between predicted and measured colors, and the corresponding 50:50% acceptability and perceptibility thresholds (AT00 and PT00) were used for performance assessment. RESULTS: The best performing optical model was the four-flux model RTE-4F-RT, with an average ΔE00 = 0.72 over all samples, 94.87% of the differences below AT00 and 65.38% below PT00. The best performing numerical model was L*a*b*-PCHIP (interpolation mode), with an average ΔE00 = 0.48, and 100% and 79.69% of the differences below AT00 and PT00, respectively. SIGNIFICANCE: Both optical and numerical models offer comparable color prediction accuracy, offering flexibility in model choice. These results help guide decision-making on prediction methods by clarifying their strengths and limitations.
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lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Neoadjuvant Therapy , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Drug Resistance, Neoplasm/genetics , Biomarkers, Tumor/genetics , Cell Line, Tumor , Gene Expression Profiling , GATA3 Transcription Factor/genetics , GATA3 Transcription Factor/metabolism , TranscriptomeABSTRACT
OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.
Subject(s)
Intensive Care Units , Respiratory Distress Syndrome , Tidal Volume , Humans , Latin America/epidemiology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/mortality , Respiration, Artificial , Respiratory Insufficiency/therapy , Respiratory Insufficiency/epidemiologyABSTRACT
In this study, thermoplastic starch (TPS) biofilms were developed using starch isolated from the seeds of Melicoccus bijugatus (huaya) and reinforced with bentonite clays at concentrations of 1%, 3%, and 5% by weight. Novelty of this research lies in utilizing a non-conventional starch source and enhancing properties of TPS through clay reinforcement. FTIR analysis verified bentonite's nature of clays, while SEM analysis provided insights into morphology and agglomeration behavior. Key findings include a notable increase in biofilm thickness and elastic modulus with higher clay content. Specifically, tensile strength of biofilms improved from 2.5 MPa for pure TPS to 5.0 MPa with 5% clay reinforcement. The elastic modulus increased from 25 MPa (TPS) to 60 MPa (5% clay). Thermal stability also showed enhancement, with initial degradation temperature increasing from 110 °C for pure TPS to 130 °C for TPS with 5% clay. Water vapor permeability (WVP) tests demonstrated a decrease in WVP values from 4.11 × 10-10 g m-1 s-1 Pa-1 for pure TPS to 2.09 × 10-10 g m-1 s-1·Pa-1 for TPS with 5% clay, indicating a significant barrier effect due to clay dispersion. These results suggest that biofilms based on huaya starch and reinforced with bentonite clay have considerable potential for sustainable food packaging applications, offering enhanced mechanical and barrier properties.
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BACKGROUND: Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. METHODS: Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. RESULTS: Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA's. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. CONCLUSIONS: This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.
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Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells.
Subject(s)
MicroRNAs , Neoplasms , Radiation Tolerance , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Radiation Tolerance/genetics , Neoplasms/radiotherapy , Neoplasms/genetics , Neoplasms/metabolism , DNA Repair , Animals , Gene Expression Regulation, Neoplastic/radiation effects , DNA DamageABSTRACT
Asthma is a common complex airway disease whose prediction of disease risk and most severe outcomes is crucial in clinical practice for adequate clinical management. This review discusses the latest findings in asthma genomics and current obstacles faced in moving forward to translational medicine. While genome-wide association studies have provided valuable insights into the genetic basis of asthma, there are challenges that must be addressed to improve disease prediction, such as the need for diverse representation, the functional characterization of genetic variants identified, variant selection for genetic testing, and refining prediction models using polygenic risk scores.
Subject(s)
Asthma , Genetic Predisposition to Disease , Genome-Wide Association Study , Genomics , Humans , Asthma/genetics , Asthma/diagnosis , Risk Assessment , Genetic TestingABSTRACT
This study explores various aspects of Metal-Organic Frameworks (MOFs), focusing on synthesis techniques to adjust pore size and key ligands and metals for crafting carrier MOFs. It investigates MOF-drug interactions, including hydrogen bonding, van der Waals, and electrostatic interactions, along with kinetic studies. The multifaceted applications of MOFs in drug delivery systems are elucidated. The morphology and structure of MOFs are intricately linked to synthesis methodology, impacting attributes like crystallinity, porosity, and surface area. Hydrothermal synthesis yields MOFs with high crystallinity, suitable for catalytic applications, while solvothermal synthesis generates MOFs with increased porosity, ideal for gas and liquid adsorption. Understanding MOF-drug interactions is crucial for optimizing drug delivery, affecting charge capacity, stability, and therapeutic efficacy. Kinetic studies determine drug release rates and uniformity, vital for controlled drug delivery. Overall, comprehending drug-MOF interactions and kinetics is essential for developing effective and controllable drug delivery systems.
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Introduction: Atrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and H. pylori antibodies in the identification of precursor lesions. Methods: We studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique. Results: Biomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for H. pylori. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723-48.799, p = 0.009); however, biomarkers showed low accuracy with histopathological study. Conclusions: In the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). H. pylori infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723-48.799, p = 0.009).
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Several risk factors were associated with mortality in patients with coronavirus disease 2019 (COVID-19) infection in intensive care units (ICU). We assessed the effect of risk factors related to the characteristics and clinical history of the population, laboratory test results, drug management, and type of ventilation on the probability of survival/discharge from the ICU. A retrospective cohort multicentric study of adults with COVID-19 admitted to the ICU between March 2020 and December 2021. Data were collected from 6 hospitals in 5 cities in Ecuador. The primary outcome was ICU survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Of those admitted to the ICU with COVID-19, (nâ =â 991), mean age was 56.76â ±â 13.14, and 65.9% were male. Regarding the primary outcome, 51.1% (nâ =â 506) died and 48.9% (nâ =â 485) survived. Of the group that died, their mean age was higher than the survivors (60.7 vs 52.60 years, respectively), and they had a higher prevalence of comorbidities such as arterial hypertension (37.2% vs 20.4%, respectively) and diabetes mellitus (26.9% vs 15.7%, respectively), with Pâ <â .001. In ventilatory management, 32.7% of patients used noninvasive ventilation and high-flow nasal cannula, and 67.3% required invasive ventilatory support. After adjusting for confounders, Cox regression analysis showed that patients were less likely to be discharged alive from the ICU if they met the following conditions: arterial hypertension (hazard ratio [HR]â =â 0.83 95% CI 0.723-0.964), diabetes mellitus (HRâ =â 0.80 95% CI 0.696-0.938), older than 62 years (HRâ =â 0.86 95% CI 0.790-0.956), obese (body mass indexâ ≥â 30) (HRâ =â 0.78 95% CI 0.697-0.887), 1 unit increase in SOFA score (HRâ =â 0.94 95% CI 0.937-0.961), PaO2/FiO2 ratio <100 mm Hg (HRâ =â 0.84 95% CI 0.786-0.914), and the use of invasive mechanical ventilation (HRâ =â 0.68 95% CI 0.614-0.769). Risk factors associated with increased mortality were older age, obesity, arterial hypertension, and diabetes. Factors such as male gender, chronic obstructive pulmonary disease, acute kidney injury, and cancer reported in other investigations did not have the same effect on mortality in our study.
Subject(s)
COVID-19 , Intensive Care Units , Humans , Male , COVID-19/mortality , COVID-19/epidemiology , Middle Aged , Female , Ecuador/epidemiology , Retrospective Studies , Intensive Care Units/statistics & numerical data , Risk Factors , Aged , Adult , Comorbidity , Hospital Mortality , SARS-CoV-2 , Respiration, Artificial/statistics & numerical data , Proportional Hazards ModelsABSTRACT
A 48-year-old woman presented to the emergency department with a one-week history of progressive dyspnea. During her hospitalization, the diagnosis of diffuse alveolar hemorrhage was made. She subsequently developed respiratory failure and acute right ventricular failure. Despite medical treatment, she continued to experience distributive shock due to a generalized inflammatory response. Circulatory support with ECMO was needed. We opted for triple cannulation to manage the multiorgan failure as a bridge to recovery. We describe our experience with an uncommon cannulation technique: veno-pulmonary-arterial cannulation, which enabled us to address cardiogenic shock, refractory hypoxemia, and distributive shock, leading to the successful recovery of the patient.
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Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.
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Three-dimensional structured illumination microscopy (3D-SIM) and fluorescence in situ hybridization on three-dimensional preserved cells (3D-FISH) have proven to be robust and efficient methodologies for analyzing nuclear architecture and profiling the genome's topological features. These methods have allowed the simultaneous visualization and evaluation of several target structures at super-resolution. In this chapter, we focus on the application of 3D-SIM for the visualization of 3D-FISH preparations of chromosomes in interphase, known as Chromosome Territories (CTs). We provide a workflow and detailed guidelines for sample preparation, image acquisition, and image analysis to obtain quantitative measurements for profiling chromosome topological features. In parallel, we address a practical example of these protocols in the profiling of CTs 9 and 22 involved in the translocation t(9;22) in Chronic Myeloid Leukemia (CML). The profiling of chromosome topological features described in this chapter allowed us to characterize a large-scale topological disruption of CTs 9 and 22 that correlates directly with patients' response to treatment and as a possible potential change in the inheritance systems. These findings open new insights into how the genome structure is associated with the response to cancer treatments, highlighting the importance of microscopy in analyzing the topological features of the genome.
Subject(s)
Imaging, Three-Dimensional , In Situ Hybridization, Fluorescence , Humans , In Situ Hybridization, Fluorescence/methods , Imaging, Three-Dimensional/methods , Translocation, Genetic , Chromosomes/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Interphase/genetics , Chromosomes, Human/genetics , Image Processing, Computer-Assisted/methodsABSTRACT
AIMS: Renal and liver congestion are associated with adverse outcomes in patients with tricuspid regurgitation (TR). Currently, there are no valid sonographic indicators of fluid status in this population. Intra-renal venous Doppler (IRVD) is a novel method for quantifying renal congestion but its interpretation can be challenging in severe TR due to altered haemodynamics. This study explores the potential of portal vein Doppler (PVD) as an alternative marker for decongestion during volume removal in patients with severe TR. METHODS AND RESULTS: Forty-two patients with severe TR undergoing decongestive therapy were prospectively enrolled. Inferior vena cava diameter, PVD, and IRVD were sequentially assessed during volume removal. Improvement criteria were portal vein pulsatility fraction (PVPF) < 70% and renal venous stasis index (RVSI) < 0.5 for partial improvement, and PVPF < 30% and RVSI < 0.2 for complete improvement. After volume removal, PVPF significantly improved from 130 ± 39% to 47 ± 44% (P < 0.001), while IRVD improved from 0.72 ± 0.08 to 0.54 ± 0.22 (P < 0.001). A higher proportion of patients displayed improvement in PVD compared to IRVD (partial: 38% vs. 29%, complete: 41% vs. 7%) (P < 0.001). Intra-renal venous Doppler only improved in patients with concomitant improvement in severe TR. Portal vein Doppler was the only predictor of achieving ≥5â L of negative fluid balance [area under the ROC curve (AUC) 0.83 P = 0.001]. CONCLUSION: This proof-of-concept study suggests that PVD is the only sonographic marker that can track volume removal in severe TR, offering a potential indicator for decongestion in this population. Further intervention trials are warranted to determine if PVD-guided decongestion improves patient outcomes in severe TR.
Subject(s)
Portal Vein , Proof of Concept Study , Tricuspid Valve Insufficiency , Humans , Portal Vein/diagnostic imaging , Male , Female , Tricuspid Valve Insufficiency/physiopathology , Tricuspid Valve Insufficiency/diagnosis , Prospective Studies , Middle Aged , Severity of Illness Index , Aged , Ultrasonography, Doppler/methods , Hemodynamics/physiology , Vena Cava, Inferior/diagnostic imagingABSTRACT
Gene-environment interactions (G × E), the interplay of genetic variation with environmental factors, have a pivotal impact on human complex traits and diseases. Statistically, G × E can be assessed by determining the deviation from expectation of predictive models based solely on the phenotypic effects of genetics or environmental exposures. Despite the unprecedented, widespread and diverse use of G × E analytical frameworks, heterogeneity in their application and reporting hinders their applicability in public health. In this Review, we discuss study design considerations as well as G × E analytical frameworks to assess polygenic liability dependent on the environment, to identify specific genetic variants exhibiting G × E, and to characterize environmental context for these dynamics. We conclude with recommendations to address the most common challenges and pitfalls in the conceptualization, methodology and reporting of G × E studies, as well as future directions.
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Asthma is a heterogeneous respiratory disease that represents a substantial social and economic burden [...].
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Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder.
Subject(s)
Cryptorchidism , Infertility , Lagomorpha , Humans , Adult , Rabbits , Male , Animals , Down-Regulation , Kynurenine , Serotonin , Testis/pathology , Infertility/pathologyABSTRACT
BACKGROUND: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. METHODS: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. RESULTS: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. CONCLUSION: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.
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The analysis of gene expression quantification data is a powerful and widely used approach in cancer research. This work provides new insights into the transcriptomic changes that occur in healthy uterine tissue compared to those in cancerous tissues and explores the differences associated with uterine cancer localizations and histological subtypes. To achieve this, RNA-Seq data from the TCGA database were preprocessed and analyzed using the KnowSeq package. Firstly, a kNN model was applied to classify uterine cervix cancer, uterine corpus cancer, and healthy uterine samples. Through variable selection, a three-gene signature was identified (VWCE, CLDN15, ADCYAP1R1), achieving consistent 100% test accuracy across 20 repetitions of a 5-fold cross-validation. A supplementary similar analysis using miRNA-Seq data from the same samples identified an optimal two-gene miRNA-coding signature potentially regulating the three-gene signature previously mentioned, which attained optimal classification performance with an 82% F1-macro score. Subsequently, a kNN model was implemented for the classification of cervical cancer samples into their two main histological subtypes (adenocarcinoma and squamous cell carcinoma). A uni-gene signature (ICA1L) was identified, achieving 100% test accuracy through 20 repetitions of a 5-fold cross-validation and externally validated through the CGCI program. Finally, an examination of six cervical adenosquamous carcinoma (mixed) samples revealed a pattern where the gene expression value in the mixed class aligned closer to the histological subtype with lower expression, prompting a reconsideration of the diagnosis for these mixed samples. In summary, this study provides valuable insights into the molecular mechanisms of uterine cervix and corpus cancers. The newly identified gene signatures demonstrate robust predictive capabilities, guiding future research in cancer diagnosis and treatment methodologies.