Skip to main content

Pancreatic Cancer

Drug Resistance Analysis of Pancreatic Cancer Based on Universally Differentially Expressed Genes


Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive malignant neoplasms, with a 12.8% five-year survival rate according to National Cancer Institute statistics. Complete surgery resection is the only possible cure for resectable PDAC, but most patients are already in an advanced stage at diagnosis. Chemotherapy with/without radiotherapy has been a mainstay strategy for treating PDAC, but it only provides a modest improvement in survival. Only 3% to 11% of patients have pathological complete responses after receiving chemotherapy with/without radiation therapy, which may be due to the high heterogeneity between patients and the ubiquitous drug resistance of PDAC.

Immune checkpoint blockade (ICB) has changed the standard of care for multiple cancers and has brought hope to pancreatic cancer patients; however, almost all tentative trials have had little effect or failed before clinical application. The most common reason for failure was the immunosuppressive tumor microenvironment (TME) resulting in low effector T cell infiltration, which is unfavorable for the immune response. We suspect that there are some common features underlying the high heterogeneity of pancreatic cancer, which could be closely related to the mechanism underlying the ineffectiveness of current therapies. It is essential to identify and target these mechanisms to improve the early diagnosis rate and therapeutic efficiency.

Conventional differentially expressed gene (DEG) screening methods for bulk tissues only compare the average expression levels between disease and control groups, which cannot show the dysregulation status of each gene in a single disease sample or the frequency of differential expression of genes in all disease samples. The gold standard for individualized DEG screening is comparing the expression levels between paired tumor and adjacent normal samples from the same patient. However, the late diagnosis and difficulty of sampling pathologically normal samples in the complicated structure of the pancreas has led to few paired samples.

To solve this problem, a robust individual DEG screening method, RankComp, has been developed to detect the dysregulation of genes in a single tumor sample relative to the normal background derived from normal samples from different studies. Thus, we can identify individual-level DEGs for unpaired tumor samples based on the aggregation of normal samples using this method. Here, we made full use of paired and unpaired PDAC samples to identify common molecular characteristics of PDAC patients to construct a robust early diagnosis model and determine the mechanisms underlying the resistance to current therapies.

In this study, using transcription profiles of paired and unpaired PDAC bulk samples, we identified individual-level DEGs in the PDAC samples and defined the genes that were dysregulated in at least 85% of the PDAC samples as universally differentially expressed genes (UDEGs). Bulk assays represent a population average, which masks the heterogeneity that exists at the single-cell level . Thus, we analyzed the expression of the UDEGs at the single-cell level to explore their roles in the formation of tumors. Finally, we investigated the potential association between the UDEGs and overall drug resistance based on GDSC resistance data, as well as their correlation with responsiveness to immunotherapy using reported immunotherapy biomarkers.

Pancreatic cancer, Pancreatitis, Pancreatic ductal adenocarcinoma, Tumor markers, CA 19-9, Chronic pancreatitis, Acute pancreatitis, Diabetes mellitus, Jaundice, Abdominal pain, Chemotherapy, Radiation therapy, Genetic mutations, KRAS mutation, Metastasis, Whipple procedure, Immunotherapy, Biliary obstruction, Pancreatic cysts, Early detection

#PancreaticCancer, #Pancreatitis, #PDAC, #TumorMarkers, #CA199, #ChronicPancreatitis, #AcutePancreatitis, #PancreaticHealth, #DiabetesAndCancer, #CancerAwareness, #PancreaticPain, #CancerResearch, #KRASMutation, #PancreaticTumor, #CancerMetastasis, #WhippleSurgery, #Immunotherapy, #CancerDiagnosis, #PancreaticScreening, #OncologyCare

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Comments

Post a Comment

Popular posts from this blog

Fruitful innovation

Fruitful innovation: Transforming watermelon genetics with advanced base editors The development of new adenine base editors (ABE) and adenine-to-thymine/ guanine base editors (AKBE) is transforming watermelon genetic engineering. These innovative tools enable precise A:T-to-G and A:T-to-T base substitutions, allowing for targeted genetic modifications. The research highlights the efficiency of these editors in generating specific mutations, such as a flowerless phenotype in ClFT (Y84H) mutant plants. This advancement not only enhances the understanding of gene function but also significantly improves molecular breeding, paving the way for more efficient watermelon crop improvement. Traditional breeding methods for watermelon often face challenges in achieving desired genetic traits efficiently and accurately. While CRISPR/Cas9 has provided a powerful tool for genome editing, its precision and scope are sometimes limited. These limitations highlight the need for more advanced gene-e...
Post a Comment
Read more

Genetic factors with clinical trial stoppage

Genetic factors associated with reasons for clinical trial stoppage Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to ...
Post a Comment
Read more

Genetic Test

Genetic test eliminates progressive retinal atrophy in English shepherd dogs Researchers at the University of Cambridge recently published their findings in Genes after identifying the genetic mutation that is causing progressive retinal atrophy (PRA) in English shepherd dogs. PRA is a group of inherited diseases causing progressive degeneration of the light sensitive cells within the back of the eyes. When it comes to PRA in dogs, they are born with normal vision but by the age of 4-5 they go totally blind with no treatment. According to the release, by identifying the canines carrying this disease before they lose vision, this can be then used as a tool to guide breeding decisions to prevent the passing of the disease onto puppies.1 Historically, owners did not realize their dog had PRA until they were middle-aged, which means it could have been passed on to puppies if they had bred, making this a hard disease to control. “Once the dog’s eyesight starts to fail there’s no treatment ...
Post a Comment
Read more