Efficacy and safety of miglustat in the treatment of GM2 gangliosidosis: A systematic review.

BACKGROUND: Since the results of previous studies regarding the safety and efficacy of miglustat in GM2 gangliosidosis (GM2g) were inconsistent, we aimed to assess miglustat therapy in GM2g patients. METHODS: This study followed the latest version of PRISMA. We included the observational or interventional studies reporting GM2g patients under miglustat therapy by searching PubMed, Web of Science, and Scopus. Data extracted included the natural history of individual patient data, as well as the safety and efficacy of miglustat in GM2g patients. The quality assessment was performed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: A total of 1023 records were identified and reduced to 621 after removing duplicates. After screening and applying the eligibility criteria, 10 articles and 2 abstracts met the inclusion criteria. Overall, the studies represented 54 patients with GM2g under treatment with miglustat and 22 patients with GM2g in the control group. Among patients with available data, 14 and 54 have been diagnosed with Sandhoff disease and Tay-Sachs disease, respectively. Patients included in this review consisted of 23 infantile, 4 late-infantile, 18 juvenile, and 31 adult-onset GM2g. CONCLUSIONS: Although miglustat should not be considered a definite treatment for GM2g, it appears that patients, particularly those with infantile or late-infantile GM2g, could benefit from miglustat therapy to some extent. We also make some suggestions regarding future studies presenting their findings in a standard format to facilitate pooling the available data in such rare diseases for a more comprehensive conclusion.

Paroxysmal hemicrania in children and adolescents: A systematic review.

OBJECTIVE: We aimed to report the accessible demographic, clinical, and radiological characteristics of reported pediatric paroxysmal hemicrania (PH). INTRODUCTION: It has been a while since PH in a child was first described. However, it is still unknown whether children's PH follows the same patterns as adults. METHODS: This study followed the latest version of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). PubMed, Web of Science, and Scopus were searched systematically without time limitation. We included all English-language, peer-reviewed articles, including observational or interventional studies reporting PH cases in children or adolescents based on the International Classification of Headache Disorders (ICHD) criteria. Data extracted included PH class; sex; age; age of onset; frequency, duration, site, severity, and quality of pains; triggers; and autonomic and migrainous symptoms, as well as a sense of restlessness/agitation, response to treatment, laboratory investigations, imaging, comorbidity, and family history. For quality assessment, two independent reviewers (MB and VM) assessed the methodological quality of the included studies through the Joanna Briggs Institute's critical appraisal checklist. RESULTS: A total of 182 records were identified and reduced to 116 after removing duplicates. After screening, 22 articles met the inclusion criteria. Overall, the studies represented 35 children or adolescents with PH. We found a boy-to-girl ratio of 1.125:1. Onset occurred at a broad range of 1 to 14 years old. The mean age of onset among reported cases in children and adolescents was 6.5 years, while the mean age of diagnosis was 8.2 years. [Correction added on 22 August 2022, after first online publication: In the preceding sentence, 6.3 and 7.9 years were changed to 6.5 and 8.2 years, respectively.] The attacks' frequency and duration were greatly varied. Left-sided pain occurred twice as often as right-sided pain. The characteristics of the pain were usually severe in intensity. In nearly all of the cases, it was accompanied by ipsilateral cranial autonomic features. While most attacks were spontaneous, there were some common triggers. The physical examination, electroencephalogram, and brain magnetic resonance imaging had normal findings. Almost all patients benefited from indomethacin and showed complete responses to treatment, while some needed combination treatment of indomethacin with other medications. CONCLUSION: Although pediatric-onset PH has similar features to adult-onset PH, there are some challenges with ICHD criteria for younger children that limit the ability to confidently assign a diagnosis. Moreover, owing to concomitant migrainous features, PH may be confused with migraine in children and adolescents.

Dental pulp stem cell transplantation ameliorates motor function and prevents cerebellar atrophy in rat model of cerebellar ataxia.

Cerebellar ataxias (CA) include a range of neurodegenerative disorders hallmarked by deterioration of the cerebellum. Cell replacement therapy (CRT) offers a potential remedy for the diseases associated with the central nervous system (CNS). This study was designed to assess the neurorestorative/protective effects of dental pulp stem cell (DPSC) implantation on a rat model of CA induced by 3-acetylpyridine (3-AP) as a neurotoxin. To begin, human DPSCs were extracted, cultured and phenotypically characterized. Then, experimental ataxia was induced in 20 male adult rats by a single injection of 3-AP and bilateral DPSC transplantation was performed 3 days after 3-AP administration, followed by stereological analysis of cerebellar layers along with assessment of motor skills and inflammatory response. The findings showed that transplantation of DPSCs in a 3-AP model of ataxia ameliorated motor coordination and muscle activity, increased cerebellar volumes of molecular and granular layers plus white matter, reduced the levels of inflammatory cytokines and thwarted the degeneration of Purkinje cells against 3-AP toxicity. Taken together, human DPSCs could be considered as a suitable candidate for CRT-based therapies with a specific focus on CA.

Optimizing the nanostructure of graphene oxide/silver/arginine for effective wound healing.

In this study, we introduce a novel graphene oxide/silver/arginine (GO/Ag/Arg) nanohybrid structure, which can act as an angiogenesis promoter and provide antibacterial nanostructure for improving the wound healing process. GO/Ag nanostructure has been optimized in terms of the GO/Ag mass ratio and pH values using central composite design and the response surface method to increase the Ag loading efficiency. Then, Arg was chemically introduced to the surface of GO/Ag nanostructure. Electrospun polycaprolactone (PCL)-GO/Ag/Arg nanocomposite was successfully fabricated and characterized. The synthesized nanocomposite demonstrated not only a great antibacterial effect on both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial species, but appropriate biocompatibility against L929 fibroblastic cell lines. The results demonstrated that the preparation of the PCL-GO/Ag/Arg nanocomposite at a concentration of 1.0 wt% GO/Ag/Arg possessed the best biological and mechanical features. In vivo experiments also revealed that the use of optimized PCL-GO/Ag/Arg nanocomposite, after 12 d of treatment, led to significant increase in the healing process and also regeneration of the wound via reconstruction of a thickened epidermis layer on the wound surface, which was confirmed by histological analysis. In conclusion, the proposed approach can introduce a novel notion for preparing antibacterial material that significantly promotes angiogenesis.

Collagen-alginate microspheres as a 3D culture system for mouse embryonic stem cells differentiation to primordial germ cells.

Germ cells differentiation of stem cells will aid treatment of adults with infertility. Biopolymers utilization provided synthetic extracellular matrix (ECM) and desired attributes in in vitro to improve conditions for stem cells attachment, proliferation and differentiation. Mixture of alginate as a biocompatible hydrogel, with collagen IV, could establish an in vitro 3 dimensional (3D) culture model. The objective of this study was investigation of the mouse ESCs differentiation capacity to putative primordial germ cells (PGCs) in the alginate and alginate-collagen IV microspheres (CAM). ESCs aggregated together to form embryoid bodies (EB) in CAM under basal medium supplemented with bone morphogenetic protein-4 (BMP4) as a differentiation factor. Viability and PGC differentiation of the stem cells in microspheres was evaluated by apoptosis and PGC related gene markers. Flow cytometry analysis was also used to detect of Mvh endogenous protein as a specific PGC marker. PGC gene and protein expression revealed that differentiation potential of ESCs to putative PGCs in CAM is significantly higher than control groups. Taking together, it was concluded that CAM demonstrated a great potential to use in PGCs differentiation and treatment of adults with infertility and may be a reliable means of producing mature germ cells.

The ability of mouse nuclear transfer embryonic stem cells to differentiate into primordial germ cells.

Nuclear transfer embryonic stem cells (ntESCs) show stem cell characteristics such as pluripotency but cause no immunological disorders. Although ntESCs are able to differentiate into somatic cells, the ability of ntESCs to differentiate into primordial germ cells (PGCs) has not been examined. In this work, we examined the capacity of mouse ntESCs to differentiate into PGCs in vitro. ntESCs aggregated to form embryoid bodies (EB) in EB culture medium supplemented with bone morphogenetic protein 4(BMP4) as the differentiation factor. The expression level of specific PGC genes was compared at days 4 and 8 using real time PCR. Flow cytometry and immunocytochemical staining were used to detect Mvh as a specific PGC marker. ntESCs expressed particular genes related to different stages of PGC development. Flow cytometry and immunocytochemical staining confirmed the presence of Mvh protein in a small number of cells. There were significant differences between cells that differentiated into PGCs in the group treated with Bmp4 compared to non-treated cells. These findings indicate that ntESCs can differentiate into putative PGCs. Improvement of ntESC differentiation into PGCs may be a reliable means of producing mature germ cells.

Gene therapy in glioblastoma multiforme: Can it be a role changer?

Glioblastoma multiforme (GBM) is one of the most lethal cancers with a poor prognosis. Over the past century since its initial discovery and medical description, the development of effective treatments for this condition has seen limited progress. Despite numerous efforts, only a handful of drugs have gained approval for its treatment. However, these treatments have not yielded substantial improvements in both overall survival and progression-free survival rates. One reason for this is its unique features such as heterogeneity and difficulty of drug delivery because of two formidable barriers, namely the blood-brain barrier and the tumor-blood barrier. Over the past few years, significant developments in therapeutic approaches have given rise to promising novel and advanced therapies. Target-specific therapies, such as monoclonal antibodies (mAbs) and small molecules, stand as two important examples; however, they have not yielded a significant improvement in survival among GBM patients. Gene therapy, a relatively nascent advanced approach, holds promise as a potential treatment for cancer, particularly GBM. It possesses the potential to address the limitations of previous treatments and even newer advanced therapies like mAbs, owing to its distinct properties. This review aims to elucidate the current status and advancements in gene therapy for GBM treatment, while also presenting its future prospects.

A review of animal models utilized in preclinical studies of approved gene therapy products: trends and insights.

Scientific progress heavily relies on rigorous research, adherence to scientific standards, and transparent reporting. Animal models play a crucial role in advancing biomedical research, especially in the field of gene therapy. Animal models are vital tools in preclinical research, allowing scientists to predict outcomes and understand complex biological processes. The selection of appropriate animal models is critical, considering factors such as physiological and pathophysiological similarities, availability, and ethical considerations. Animal models continue to be indispensable tools in preclinical gene therapy research. Advancements in genetic engineering and model selection have improved the fidelity and relevance of these models. As gene therapy research progresses, careful consideration of animal models and transparent reporting will contribute to the development of effective therapies for various genetic disorders and diseases. This comprehensive review explores the use of animal models in preclinical gene therapy studies for approved products up to September 2023. The study encompasses 47 approved gene therapy products, with a focus on preclinical trials. This comprehensive analysis serves as a valuable reference for researchers in the gene therapy field, aiding in the selection of suitable animal models for their preclinical investigations.

The progressive trend of modeling and drug screening systems of breast cancer bone metastasis.

Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites.The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials' chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.

Knowledge, Attitude, and Practice toward Skin Cancer among Patients of Dermatology Clinics and Medical Students/General Practitioners.

This cross-sectional study assessed the knowledge, attitude, and practices (KAP) regarding skin cancer among dermatology clinic patients, medical students, and general practitioners (GPs) in Tehran, Iran. The researchers collected data using a validated questionnaire administered online, measuring KAP on scales of 0-31, 0-16, and 0-28, respectively, with scores above 16, 8, and 14 indicating "good" levels. Of 2243 participants (mean age 28 years), 59.4% had good knowledge, 19.8% had good attitudes, 31.8% had good practices, and 29.8% had good overall KAP. Medical students/GPs scored higher on knowledge and attitudes, while patients scored better on practices. Knowledge, attitudes, and practices were positively correlated in professionals but inversely correlated in patients. The findings suggest that while knowledge was moderate, attitudes and behaviors remained poor, particularly among patients. Immediate interventions are needed to improve attitudes and prevention practices, as public health initiatives must focus on positively influencing both to translate knowledge into meaningful action and find the reasons why good knowledge may not always lead to good practice. These findings underline the need for targeted interventions to bridge the gap between knowledge and preventive behaviors, to effectively reduce the burden of skin cancer in the population.

Inflammation and immunological disarrays are associated with acute exercise in type 2 diabetes.

Objective: Type 2 diabetes (T2D) is the most common metabolic disorder that is associated with insulin resistance. The aim of the present study is to discover details of the molecular mechanism of exercise on control or progress of diabetic condition in patients via network analysis. Methods: Gene expression profiles of patients with T2D before and after doing exercise are retrieved from Gene Expression Omnibus (GEO) and are pre-evaluated by the GEO2R program. Data are studied based on expression values, regulatory relationships between the differentially expressed genes (DEGs), gene ontology analyses, and protein-protein interaction PPI network analysis. Results: A number of 118 significant DEGs were identified and classified based on fold change (FC) values as most dysregulated genes and dysregulated individuals. Action map analysis revealed that 18 DEGs appeared as the critical genes. Gene ontology analysis showed that 24 DEGs are connected to at least four pathways. JUN, IL6, IL1B, PTGS2, FOS, MYC, ATF3, CXCL8, EGR1, EGR2, NR4A1, PLK3, TTN, and UCP3 were identified as central DEGs. Conclusion: Finally; JUN, IL6, IL1B, PTGS2, FOS, ATF3, CXCL8, EGR1, and EGR2 were introduced as the critical targeted genes by exercise. Since the critical genes after exercise are upregulated and mostly are known as the risk factors of T2D, it can be concluded that unsuitable exercise can develop diabetic conditions in patients. Acute exercise-induced inflammation and immune disturbances seem to be associated with the development of T2D in patients.

X-Linked Retinitis Pigmentosa Gene Therapy: Preclinical Aspects.

The most common inherited eye disease is retinitis pigmentosa (RP). X-linked RP (XLRP) is one of the most severe types of RP, with a considerable disease burden. Patients with XLRP experience a decrease in their vision and become blind in their 4th decade of life, causing much morbidity after starting a rather normal life. Treatment of XLRP remains challenging, and current treatments are not effective enough in restoring vision. Gene therapy of XLRP, capable of restoring the functional RPGR gene, showed promising results in preclinical studies and clinical trials; however, to date, no approved product has entered the market. The development of a gene therapy product needs through preliminary assessment of the drug in animal models before administration to humans. In this article, we reviewed the genetic pathology of XLRP, along with the preclinical aspects of the XLRP gene therapy, animal models, associated assessments, and future challenges and directions.

Vertical transmission and maternal passive immunity post-SARS-CoV-2.

Since 2020, the highly contagious nature and various transmission routes of SARS-CoV-2 have rendered the pandemic interminable. Vertical transmission (VT) through the placenta and breast milk, which is frequent for certain virus types, is thought to exist for SARS-CoV-2 and is hypothesized by many researchers. Conversely, antibodies are produced to counteract the effect of viruses. Since newborns' immunologic system cannot produce proper antibodies, maternal antibodies are usually transferred from mother to infant/fetus to meet the need. This theory leads to the hypothesis of transmission of antibodies through the placenta and breast milk following SARS-CoV-2 infection or vaccination. This paper further discusses these hypotheses, considering consequences of fetus/infant harm versus benefit.

Introducing Albumin and Interleukin 6 as Common Critical Dysregulated Proteins Between Migraine and Gliosarcoma.

Introduction: It is reported that migraine may be a risk factor for brain cancers. Since one of the best ways to assess this possible relationship is to study the molecular mechanism, here the common central dysregulated proteins between these diseases are investigated via network analysis. Methods: The dysregulated proteins of migraine and gliosarcoma are extracted from the STRING database and interacted via Cytoscape software, version 3.7.2. to form two separate networks. Central nodes of the networks are compared to find the common central district proteins. First neighbors of the common central proteins are studied. Results: The number of 11 hub bottlenecks was identified for each of the migraine and gliosarcoma cancer networks. Albumin (ALB) and interleukin 6 (IL6) were introduced as common differentially expressed central proteins. Kininogen 1 (KNG1), vascular endothelial growth factor A (VEGFA), and neurofibromatosis type I (NF1) the first neighbors of ALB-IL6 were connected to the central nodes of networks of the two studied diseases. Conclusion: ALB and IL6 can be considered molecular links between migraine and brain cancers. Highlights: Differentially expression of albumin (ALB) and interleukin 6 (IL6) is highlighted as the common key events in migraine and gliosarcoma.Kininogen 1 (KNG1), vascular endothelial growth factor A (VEGFA), and neurofibromatosis type I (NF1) are introduced as possible critical players in migraine and gliosarcoma.Based on four centrality parameters, ALB is characterized with stronger centrality properties relative to IL6. Plain Language Summary: Migraine is considered as a possible risk factor for brain cancers. Therefor exploring of relationship between brain cancers and migraine is attracted attention of researchers. Understanding of diseases molecular mechanism is an important tool to better diagnosis and therapy of the studied disorders. In the present study, the common features of molecular events in migraine and gliosarcoma are studied based on protein expression changes. Analysis indicates that a few numbers of proteins play critical roles in migraine and gliosarcoma. ALB, IL6, KNG1, VEGFA, and NF1 are highlighted as the key proteins which are dysregulated in the two studied diseases. Prominent role of ALB in development of cancers is pointed out by several researchers. Important role of IL6 in promotion of migraine is disused in the previous documents. Since some diseases are risk factors for the other disorders, understanding the common features of two diseases can provide suitable therapeutic protocol to prevent development of diseases. Our finding can be used to provide suitable procedure to prevent conversion of migraine to brain cancer.

Application of nano-radiosensitizers in combination cancer therapy.

Radiosensitizers are compounds or nanostructures, which can improve the efficiency of ionizing radiation to kill cells. Radiosensitization increases the susceptibility of cancer cells to radiation-induced killing, while simultaneously reducing the potentially damaging effect on the cellular structure and function of the surrounding healthy tissues. Therefore, radiosensitizers are therapeutic agents used to boost the effectiveness of radiation treatment. The complexity and heterogeneity of cancer, and the multifactorial nature of its pathophysiology has led to many approaches to treatment. The effectiveness of each approach has been proven to some extent, but no definitive treatment to eradicate cancer has been discovered. The current review discusses a broad range of nano-radiosensitizers, summarizing possible combinations of radiosensitizing NPs with several other types of cancer therapy options, focusing on the benefits and drawbacks, challenges, and future prospects.

Decoding the expression pattern of MUC3A in gastric adenocarcinoma: unveiling the key to successful immunotherapy.

AIMS: Despite the promise of immunotherapy for gastric adenocarcinoma, resistance is common, necessitating the validation of new targets. Based on our previous bioinformatics analysis, the MUC3A antigen emerged as a promising candidate for immunotherapy against gastric adenocarcinoma. However, a comprehensive understanding of its expression at protein level remains elusive, despite its crucial role in determining clinical response. We also sought to establish a connection between the expression pattern and relevant clinical variables of the disease, whenever feasible. METHODS: Immunohistochemistry was used to determine the percentage of MUC3A-positive tumor cells in primary (PT) and metastatic tumor (MT) sites of 190 gastric adenocarcinoma patients. We also evaluated the association between MUC3A expression and variables such as Lauren classification, history of neoadjuvant chemotherapy and/or radiotherapy, and overall patient survival. RESULTS: Median MUC3A expression was 50% in PT and 70% in MT sites, exhibiting a positive correlation. MT intestinal type showed significantly higher MUC3A expression compared to other types. Neoadjuvant therapy history did not affect MUC3A expression. Higher MUC3A expression correlated with improved survival. CONCLUSIONS: Based on our previous bioinformatics data and the consistently high expression of MUC3A on gastric tumor cells, we propose advancing experimental aspects of anti-MUC3A immunotherapy for gastric adenocarcinoma.

Cell-free therapy based on extracellular vesicles: a promising therapeutic strategy for peripheral nerve injury.

Peripheral nerve injury (PNI) is one of the public health concerns that can result in a loss of sensory or motor function in the areas in which injured and non-injured nerves come together. Up until now, there has been no optimized therapy for complete nerve regeneration after PNI. Exosome-based therapies are an emerging and effective therapeutic strategy for promoting nerve regeneration and functional recovery. Exosomes, as natural extracellular vesicles, contain bioactive molecules for intracellular communications and nervous tissue function, which could overcome the challenges of cell-based therapies. Furthermore, the bioactivity and ability of exosomes to deliver various types of agents, such as proteins and microRNA, have made exosomes a potential approach for neurotherapeutics. However, the type of cell origin, dosage, and targeted delivery of exosomes still pose challenges for the clinical translation of exosome therapeutics. In this review, we have focused on Schwann cell and mesenchymal stem cell (MSC)-derived exosomes in nerve tissue regeneration. Also, we expressed the current understanding of MSC-derived exosomes related to nerve regeneration and provided insights for developing a cell-free MSC therapeutic strategy for nerve injury.

Collagen Synthesis as a Prominent Process During the Interval between Two Laser Sessions.

Introduction: Many people suffer from skin photodamage, especially photoaging. The application of a laser to repair damages is a common therapeutic method that is used widely. In the present study, the effectiveness and molecular mechanism of an Er:Glass non-ablative fractional laser on the human skin was assessed via bioinformatics and network analysis. Methods: The gene expression profiles of 17 white female forearm skins which received an Er:Glass non-ablative fractional laser before and after laser treatment in two sessions were extracted from Gene Expression Omnibus (GEO). Data were evaluated via GEO2R and the significant differentially expressed genes (DEGs) were assessed via protein-protein interaction (PPI) network analysis. The central nodes were identified and discussed for the compared set of samples. Results: Five classes of samples were clustered in two categories: first, baseline, 7 and 14 days after the first session of laser treatment, and second, one day after the first laser session, 29 days after the first laser session, and 1 day after the second laser session. The gross cell functions such as cell division and cell cycle and immune response were highlighted as the early affected targets of the laser. Collagen synthesis was resulted after the first laser session. Conclusion: In conclusion, the time interval between laser sessions plays a critical role in the effectiveness of laser therapy. Findings indicate that the gross effect of laser application appears in a short time, and important processes such as collagen synthesis happen later.

Introducing Critical Genes in Response to Photodynamic Therapy: A Network Analysis.

Introduction: Photodynamic therapy (PDT) is applied as an efficient method for preventing the progress of cancers. Light and a photosensitive compound which is known as photosensitizer (PS) are the main parts of PDT. In the present study, molecular events after using PDT in the presence of a super lethal dose of a PS were assessed via protein-protein interaction (PPI) analysis. Methods: Data were extracted from Gene Expression Omnibus (GEO). The gene expression profiles of the treated human Sk-Cha1 cells via PDT were compared with the control cells. Expressed change analysis and PPI network analysis were administrated via Cytoscape software v 3.7.2 to find the critical differentially expressed genes (DEGs). Regulatory relationships between the central DEGs were evaluated and the highlighted genes were identified. Results: The significant amounts of gene expression values were grouped and a few DEGs characterized by tremendously expressed values were identified. EGFR, CANX, HSPA5, MYC, JUN, ITGB1, APP, and CDH1 were highlighted as hub-bottleneck DEGs. EGFR, CDH1, and JUN appeared as a set of SEGs, which play a crucial role in response to PDT in the treated Sk-Cha1 cells. Conclusion: In conclusion, regulatory relationships between EGFR, CDH1, and JUN, which have an effect on the regulation of cellular survival, differentiation, and proliferation, were highlighted in the present investigation.

Extracellular matrix is the main targeted environment in early stage of pancreatic ductal adenocarcinoma.

Aim: Due to weak diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC), detection of PDAC possible biomarkers in early stage is the main aim of this study. Background: PDAC is known as an exocrine cancer with a 5-year overall survival of 11%. Methods: Gene expression profiles of early stage of PDAC tissue and normal tissue are downloaded from gene expression omnibus (GEO) and evaluated via GEO2R. The significant differentially expressed genes (DEGs) are investigated via protein-protein interaction (PPI) network analysis and gene ontology. Results: Among 104 DEGs, ALB, COL1A1, COL1A2, MMP1, POSTN, PLAU, and COL3A1 were pointed out as hub nodes. "Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13" group of 52 biological terms were identified as the main affected terms. Conclusion: In conclusion, ALB, MMP1, and COL1A1 genes were highlighted as possible biomarkers of early stage of PDAC. Dysfunction of extracellular matrix was identified as a main event in patients.