Biochemical Genetics最新文献

{"title":"Identification and Verification of Potential Markers Related to Myocardial Fibrosis by Bioinformatics Analysis.","authors":"Jiazhuo Huang, Zhentao Shi, Zhifeng Huang, Shaobin Lai","doi":"10.1007/s10528-024-10937-9","DOIUrl":"https://doi.org/10.1007/s10528-024-10937-9","url":null,"abstract":"<p><p>Mounting evidence indicates that myocardial fibrosis (MF) is frequently intertwined with immune and metabolic disorders. This comprehensive review aims to delve deeply into the crucial role of immune-related signature genes in the pathogenesis and progression of MF. This exploration holds significant importance as understanding the underlying mechanisms of MF is essential for developing effective diagnostic and therapeutic strategies. The dataset GSE9735 about myocardial fibrosis and non-fibrosis was downloaded from GEO database. Differentially expressed genes (DEGs) were identified by 'limma' package in R software. Then, the biological function of DEG was determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. XCell was used to estimate the composition pattern of matrix and immune cells. Protein-protein interaction (PPI) network was constructed based on STRING analysis software, and Hub genes were screened and functional modules were analyzed. The correlation between hub genes and immune cell subtypes was analyzed. Hub genes with |correlation coefficient|> 0.45 and p-value < 0.05 were used as characteristic biomarkers. Finally, the logistic regression model is used to verify the three markers in the training set and verification set (GSE97358 and GSE225336). A total of 635 DEGs were identified. Functional enrichment analysis shows that inflammation and immune response, extracellular matrix and structural remodeling play an important role in the pathological mechanism of MF. Immune cell infiltration analysis showed that immune cells (Plasma cells, Eosinophils, Chondrocytes and Th2 cells) significantly changed in MF pathological conditions. In PPI network analysis, IL1β, TTN, PTPRC, IGF1, ALDH1A1, CYP26A1, ALDH1A3, MYH11, CSF1R and CD80 were identified as hub genes, among which IL1β, CYP26A1 and GNG2 were regarded as immune-related characteristic markers. The AUC scores of the three biomarkers are all above 0.65, which proves that they have a good discrimination effect in MF. In this study, three immune-related genes were identified as diagnostic biomarkers of MF, which provided a new perspective for exploring the molecular mechanism of MF. This study takes a comprehensive approach to understanding the intricate relationship between myocardial fibrosis and immune metabolism. By identifying key immune-related biomarkers, this study not only reveals the molecular basis of myocardial fibrosis but also paves the way for the development of novel diagnostic tools and therapeutic strategies. These findings are critical for improving patient prognosis and may have broader implications for studying and treating other cardiovascular diseases associated with immune dysregulation.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycyrrhizic Acid Inhibits Hippocampal Neuron Apoptosis by Activating the PI3K/ AKT Signaling Pathway.","authors":"Guanglei Fu, Xuedi Kang, Songjun Lin","doi":"10.1007/s10528-024-10936-w","DOIUrl":"https://doi.org/10.1007/s10528-024-10936-w","url":null,"abstract":"<p><p>Glycyrrhizic acid (GA), one of the main active substances in Glycyrrhiza, has anti-inflammatory, anti-viral, and neuroprotective effects. GA can significantly reduce cerebral infarction size in middle cerebral artery occlusion (MCAO) rats and suppress inflammatory responses. However, the underlying mechanism by which GA protects the neuronal system remains poorly understood. Cell proliferation and viability were tested using CCK-8 and Edu assays. The effects of GA on apoptosis were detected using flow cytometry and Tunel assays. Western blotting was performed to assess protein expression. Behavioral experiments were conducted using the Morris water maze and rotation tests. Infarct size was observed using TTC staining. We report that GA protects neurons by inhibiting apoptosis, mainly through the PI3K/AKT pathway in oxygen-glucose deprivation/reoxygenation (OGD/R) and MCAO rat models. GA increases the viability and proliferation of oxygen- and glucose-deprived hippocampal neurons. Hippocampal neuron apoptosis decreased after GA treatment in vitro and in vivo. Furthermore, we determined that GA treatment increased the active state of PI3K and its downstream protein p-AKT, whereas when using a specific inhibitor of PI3K, Y294002, the levels of p-PI3K and p-AKT decreased. Finally, we showed that GA treatment improved spatial memory and motor coordination in MCAO rats, while TTC staining showed that GA decreased cerebral infarct size in MCAO rats. We reveal that GA protects hippocampal neurons by inhibiting their apoptosis, mainly through the PI3K/AKT signaling pathway.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allelic Diversity and Development of Breeder-Friendly Marker Specific to floury2 Gene Regulating the Accumulation of α-Zeins and Essential Amino Acids in Maize Kernel.","authors":"Hriipulou Duo, Rashmi Chhabra, Vignesh Muthusamy, Suman Dutta, Ashvinkumar Katral, Govinda Rai Sarma, Gulab Chand, Subhra J Mishra, Rajkumar U Zunjare, Firoz Hossain","doi":"10.1007/s10528-024-10935-x","DOIUrl":"https://doi.org/10.1007/s10528-024-10935-x","url":null,"abstract":"<p><p>Maize zeins lack essential amino acids, such as methionine, lysine, and tryptophan. The floury2 (fl2) mutation reduces zein synthesis and increases methionine and lysine content in kernels. In this study, fl2 gene (1612 bp) was sequenced in eight wild-type and two mutant inbreds and detected 218 SNPs and 18 InDels. Transversion of C to T at 343 bp position caused the substitution of alanine by valine in the fl2 mutant. A PCR-based marker (FL-SNP-CT) was developed, which distinguished the favorable mutant fl2 allele (T) from the wild-type (C) Fl2 allele. Gene-based diversity analysis using seven gene-based InDel markers grouped 48 inbred lines into three major clusters, with an average genetic dissimilarity coefficient of 0.534. The average major allele frequency, gene diversity, heterozygosity, and polymorphism information content of the InDel markers were 0.701, 0.392, 0.039, and 0.318, respectively. Haplotype analysis revealed 29 haplotypes of fl2 gene among these 48 inbreds. Amino acid substitution (Ala-Val) at the signal peptide cleavage site produced unprocessed 24-kDa mutant protein instead of 22-kDa zein found in normal genotype. Eight paralogues of fl2 detected in the study showed variation in exon lengths (616-1170 bp) and translation lengths (135-267 amino acids). Orthologue analysis among 15 accessions of Sorghum bicolor and two accessions of Saccharum spontaneum revealed a single exon in fl2 gene, ranging from 267 to 810 bp. The study elucidated the molecular basis of fl2 mutation and reported a breeder-friendly marker for molecular breeding programs. This is the first study to characterize fl2 gene in a set of subtropically adapted inbreds.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Complementarity of Blood-Sourced, Breast Cancer-Related TCR CDR3s and the CMV UL29 and IE1 Antigens is Associated with Worse Overall Survival.","authors":"Pooja Neerumalla, Rahul Jain, Michael T Aboujaoude, Tabitha R Hudock, Joanna J Song, Bryan H Cao, Andrea Chobrutskiy, Boris I Chobrutskiy, George Blanck","doi":"10.1007/s10528-024-10934-y","DOIUrl":"https://doi.org/10.1007/s10528-024-10934-y","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) infection is common and becomes a particular concern in immunocompromised patients. Understanding the potential role CMV plays in breast cancer patients' disease progression is important for providing more patient-specific treatments. In this study, we analyzed whether a breast cancer patient's blood-sourced T-cell receptor (TCR) complementarity determining-3 (CDR3) amino acid (AA) sequences could provide an indication of the impact of a systemic CMV infection. Specifically, we assessed the chemical complementarity of patient TCR CDR3 AAs and CMV antigens to determine whether patients with greater complementarity also represented different survival probabilities. Initially, we examined five distinct CMV antigens, of which two, IE1 and UL29, represented TCR (TRA+ RB)-CDR3-CMV antigen complementarity scores (CSs) whereby cases representing the upper 50th percentile of CSs had a worse overall survival (log-rank p = 5.034E-3, for IE1). Then, an analysis of CSs representing previously identified, TCR IE1 epitopes indicated that greater TRB CDR3-IE1 epitope complementarities represented a worse OS (log-rank p = 0.0111). These results raise the question of whether a systemic, anti-CMV response leads to increased systemic inflammation, which is either directly or indirectly supportive of tumor growth; or are patients succumbing to a direct impact of CMV functions on tumor growth or metastasis?</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Mitochondrial-Related Gene Signature for the Prediction of Prognosis and Therapeutic Efficacy in Lower-Grade Glioma.","authors":"Jingyi Yang, Lei Shen, Jiabin Zhou, Ji Wu, Chuqiao Yue, Tiansheng Wang, Songshan Chai, Yuankun Cai, Dongyuan Xu, Yu Lei, Jingwei Zhao, Yixuan Zhou, Zhimin Mei, Nanxiang Xiong","doi":"10.1007/s10528-024-10928-w","DOIUrl":"https://doi.org/10.1007/s10528-024-10928-w","url":null,"abstract":"<p><p>Lower-grade glioma (LGG) is a common primary brain tumor with a highly heterogeneous clinical presentation, and its prognosis cannot be accurately predicted by current histopathology. It has been found that mitochondria play an important role in hypoxia, angiogenesis, and energy metabolism in glioma, and mitochondrial function may have an important impact on LGG prognosis. The goal of this study was to develop a novel prognostic model based on Mitochondrial-related genes (MRGs). We first analyzed the somatic alterations profiles of MRGs in patients with LGG and found that somatic alterations were common in LGG and correlated with prognosis. Using RNA-seq data from TCGA and CGGA, 12 prognosis-related MRGs were identified to construct a mitochondrial activation score (MiAS) model by combining univariate regression and LASSO regression analysis. The model and nomogram were evaluated using the area under the ROC curve with AUC = 0.910. The model was closely correlated with the clinical characteristics of LGG patients and performed well in predicting the prognosis of LGG patients with significantly shorter overall survival (OS) time in the high-MiAS group. GSVA and GSEA results showed that oxidative stress, pro-cancer, and immune-related pathways were significantly enriched in the high-MiAS group. CIBERSORT results showed that MiAS was significantly associated with immune cell infiltration in LGG. Macrophage M1 and follicular helper T cells had increased infiltration in the high-MiAS group. TIDE predicted a better immunotherapy outcome in patients in the low-MiAS group. Finally, using data from the CTRPv2 and GDSC2 datasets to assess chemotherapy response in LGG, it was predicted that the chemotherapeutic agents AZD6482, MG-132, and PLX-4720 might be potential agents for patients in the high-MiAS group of LGG. In addition, we performed in vitro experiments and found that knockdown of OCIAD2 expression reduced the abilities of glioma cells to proliferate, migrate, and invade. In contrast, overexpression of OCIAD2 enhanced these abilities of glioma cells. This study found that MRGs were correlated with LGG patient prognosis, which is expected to provide new treatment strategies for LGG patients with different MiAS.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: MiR-485-3p/MiR-543/MiR-337-3p is Required for the Oncogenic Potential of the Hsa_circ_0007385-MEMO1 Axis in Colorectal Cancer.","authors":"Junfeng Yin, Guanglan Liu, Xinguo Zhu","doi":"10.1007/s10528-024-10900-8","DOIUrl":"10.1007/s10528-024-10900-8","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"4237"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification ATP5F1D as a Biomarker Linked to Diagnosis, Prognosis, and Immune Infiltration in Endometrial Cancer Based on Data-Independent Acquisition (DIA) Analysis.","authors":"Yuemei Cheng, Xiaolei Liang, Xuehan Bi, Chang Liu, Yongxiu Yang","doi":"10.1007/s10528-023-10646-9","DOIUrl":"10.1007/s10528-023-10646-9","url":null,"abstract":"<p><p>In developed countries, endometrial cancer (EC) is the most prevalent gynecological cancer. ATP5F1D is a subunit of ATP synthase, as well as an important component of the mitochondrial electron transport chain (ETC). ETC plays a compelling role in carcinogenesis. To date, little is known about the role of ATP5F1D in EC. We undertook data-independent acquisition mass spectrometry (DIA-MS) of 20 EC patients, comprising 10 high-grade and 10 low-grade cancer tissues. Biological functions of differentially expressed genes (DEGs) were analyzed by GO and KEGG. The expression level, clinicopathological features, diagnostic potency, prognostic value, RNA modifications, immune characteristics, and therapy response of ATP5F1D were investigated. In total, 77 DEGs were acquired by DIA analysis, which were closely related to regulating immune response and metabolic pathways. Among the five genes (NDUFB8, SLC26A2, RAF1, ATP5F1D, and GSTM5) involving in reactive oxygen species pathway, ATP5F1D showed the most significant differential expression (2.903-fold change). We found ATP5F1D had a high diagnostic value and was associated with a favorable prognosis in EC patients. After analyzing the RNA modifications of ATP5F1D, revealing a negative regulation between them. Additionally, ATP5F1D was closely related to tumor immune infiltration. Our results suggested T-cell dysfunction and TAM-M2 polarization might be the important mechanisms of ATP5F1D to facilitate tumor immune escape. Noticeably, EC patients with ATP5F1D-high expression had better immune treatment responses and were more sensitive to chemotherapy drugs. ATP5F1D can be used as a biomarker for diagnosis, prognosis, and immune infiltration of EC, and offers a crucial reference for personalized treatment of EC patients.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"4215-4236"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Intestinal TLR4 Gene Expression and Functional Verification in Lepus yarkandensis and Oryctolagus cuniculus.","authors":"Liukai Zhang, Dingwei Shao, Junyao You, Penggang Liu, Fang Deng, Jianping Zhang","doi":"10.1007/s10528-024-10925-z","DOIUrl":"https://doi.org/10.1007/s10528-024-10925-z","url":null,"abstract":"<p><p>Lepus yarkandensis live year-round in harsh desert environments and are less susceptible to enteritis. The living conditions of Oryctolagus cuniculus in captivity were suitable, but they were highly susceptible to death by Gram-negative bacteria infected with inflammatory bowel disease complex.TLR4 is closely related to the occurrence of enteritis, and the neighbor-joining topology based on the 12S rDNA sequences showed that the relationship between O. cuniculus and L. yarkandensis is as high as 98%.Therefore, we chose O. cuniculus and L. yarkandensis for comparative study.The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) in the regulation of immunity and inflammation in the intestinal tract of L. yarkandensis. In this study, the TLR4 gene was cloned for the first time in the colon of L. yarkandensis. The expression of TLR4 in the intestinal tissues of L. yarkandensis and O. cuniculus was detected by histological observation, real-time fluorescence quantification PCR(qRT-PCR), and protein blotting (Western blot).An LPS-induced cell inflammation model was constructed in vitro, and ELISA was used to examine the effect of pEGFP-N1-TLR4 and siRNA knockout on the anti-inflammatory ability of the TLR4 gene. The results showed that the open reading frame of the L. yarkandensis TLR4 gene was 2520 bp in length. Compared with the sequence of O. cuniculus, there were 15 differences in the TLR4 amino acid sequence of L. yarkandensis, 12 of which occurred in the LRR domain and 2 in the TIR domain, and the sequence changed from G to D at position 298. Immunohistochemistry showed that TLR4 was mainly expressed in the epithelial cells of the colon L. yarkandensis, and the expression level of TLR4 in the cecum and colon was significantly lower compared with that of O. cuniculus. qRT-PCR and Western blot results showed that the expression level of TLR4 in the colon of L. yarkandensis was significantly lower than that of O. cuniculus. At the cellular level, ELISA showed that overexpression of the TLR4 protein in L. yarkandensis could reduce the LPS-induced inflammatory response. Therefore, according to the above results, the protein structure and function of L. yarkandensis TLR4 may be different due to the change of nucleotide, which affects its binding with LPS and the activation of downstream molecules, so that L. yarkandensis is not prone to enteritis and can adapt to the harsh desert environment for a long time. This study also laid the foundation for improving the disease resistance of O. cuniculus and promoting the development and utilization of genes in L. yarkandensis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of the AVPR1A RS1 Microsatellite Locus with the Level of Hormones of the Anterior Pituitary Gland and Personality Traits.","authors":"Sergey S Nakhodkin, Nikolay A Barashkov, Anastasiya V Kazantseva, Vera G Pshennikova, Alena A Nikanorova, Elza K Khusnutdinova, Sardana A Fedorova","doi":"10.1007/s10528-024-10933-z","DOIUrl":"https://doi.org/10.1007/s10528-024-10933-z","url":null,"abstract":"<p><p>The arginine vasopressin receptor gene (AVPR1A) is one of the genes affecting mental processes. The aim of this study was to search for associations of microsatellite locus RS1, which is related to the AVPR1A expression level, with the level of hormones of the anterior pituitary gland and personality traits. The study sample included Yakut men aged 18-26 years (n = 121). The analysis of RS1 locus was carried out using the PCR method and sequencing of the primary nucleotide sequence. Serum hormonal levels of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin were determined by the time-resolved fluorescence immunoassay (DELFIA), plasma adrenocorticotropic hormone (ACTH) levels were determined by enzyme-linked immunosorbent assay (ELISA). In the Yakut population \"short\" (S) alleles of the AVPR1A RS1 locus containing ≤ 10 repeats (63%) and the corresponding SS genotypes (44.6%) were more frequent, while individuals with \"long\" (LL) and \"heterozygous\" (SL) genotypes accounted for 18.2 and 37.2%, respectively. The range of concentrations of ACTH and TSH in the group of SS genotype carriers was significantly lower than that observed in the group of LL genotype carriers (p = 0.042 and p = 0.048, respectively); the LH level was significantly higher (p = 0.029). The trend towards higher neuroticism in SS genotype carriers compared to the individuals with LL genotypes (p = 0.05) is revealed. The results obtained indicate the modulating effect of genetic variants of the AVPR1A gene on the level of anterior pituitary hormones, which could slightly affect the level of neuroticism in humans.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Biomarkers to Predict Early Diagnosis of Inflammatory Bowel Disease and Its Progression to Colorectal Cancer.","authors":"Farhat Khan, Naaziyah Abdulla, Thea-Leonie du Plessis, Kay Karlsson, Peter Barrow, Brendan Bebington, Liang Gu, Mandeep Kaur","doi":"10.1007/s10528-024-10917-z","DOIUrl":"https://doi.org/10.1007/s10528-024-10917-z","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) has become a common global health problem as prevalence continues to rise. It is often associated with increased risk of colorectal cancer (CRC) development. Limitations in current IBD biomarker-based diagnosis hinder the accuracy of early detection of CRC progression. Therefore, in this study, we proposed the use of transcription factor (TF)-based biomarkers that can potentially detect the transition of IBD to CRC. Various bioinformatic analysis and online database validations, and RT-qPCR validations were performed to identify possible diagnostic TFs. RUNX1 was identified as a promising TF that regulates 106 IBD/CRC-related genes. The incorporation of RUNX1 in combination with currently known IBD biomarkers, FEV + NFKB1 + RELA, achieved a comparable sensitivity and specificity scores of 99% and 87%, respectively, while RUNX1 in combination with known CRC markers, CEA + TIMP1 + CA724 + CA199, achieved a sensitivity and specificity score of 97% and 99%, respectively. Furthermore, a small pilot RT-qPCR-based analysis confirmed a demarcated shift in expression profiles in CA724, CEA, RUNX1 and TIMP1 in IBD patients compared to CRC patients' tissue samples. Specifically, CA724 is noticeably elevated in IBD, while the levels of CEA, RUNX1 with TIMP1 are probable genes that may be employed in discerning IBD progression to CRC. Therefore, these preliminary results once validated in large patient cohorts could potentially have a significant impact on CRC disease stratification, resulting in a more precise prediction for treatment and treatment outcomes, especially in South African patients.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}