In recent decades, there has been mounting evidence linking Excision repair cross-complementing gene (ERCC1) polymorphisms to colorectal cancer (CRC). According to recent epidemiological research, the ERCC1 polymorphism may have an impact on the incidence of colorectal cancer (CRC). However, there is controversy on ERCC1 genetic variants affecting CRC in these studies. Hence, this meta-analysis study aimed to analyze the link between CRC and ERCC1 gene polymorphism.
Methodology
We looked up information on the impact of ERCC1 genetic variations on CRC development in the Web of Science, PubMed, and Embase. Addressing the risk of colorectal cancer associated with mutations in the ERCC1 gene, no meta-analysis was conducted. Using Stata (version 12.0) applications, we effectively conducted a meta-analysis of thirteen case-control investigations and integrated the pooled odds ratios (ORs) according to a 95 % confidence interval (CI) of the overall and subgroup analysis.
Results
According to our findings, there appears to have been a noteworthy association found between rs3212986 and the risk of CRC in both the allele genetic model (OR 95 % CI = 1:44 (1.21–1.71) and the dominant genetic model (OR 95 % CI = 1:04 (0.93–1.15) for overall CRC.
Conclusion
In conclusion, the results of this meta-analysis showed that rs3212986 polymorphism was significantly associated with colorectal cancer risk, whereas rs11615 polymorphism was not significantly associated with colorectal cancer risk.
{"title":"Exploring the relationship between ERCC1 polymorphisms and colorectal cancer risk: Insights from an in-depth meta-analysis","authors":"Praveen Kumar Kampalli , Mohan Krishna Ghanta , Henu Kumar Verma , Afroz Alam , Sujatha Peela , LVKS Bhaskar","doi":"10.1016/j.humgen.2024.201361","DOIUrl":"10.1016/j.humgen.2024.201361","url":null,"abstract":"<div><h3>Introduction</h3><div>In recent decades, there has been mounting evidence linking Excision repair cross-complementing gene (ERCC1) polymorphisms to colorectal cancer (CRC). According to recent epidemiological research, the ERCC1 polymorphism may have an impact on the incidence of colorectal cancer (CRC). However, there is controversy on ERCC1 genetic variants affecting CRC in these studies. Hence, this meta-analysis study aimed to analyze the link between CRC and ERCC1 gene polymorphism.</div></div><div><h3>Methodology</h3><div>We looked up information on the impact of ERCC1 genetic variations on CRC development in the Web of Science, PubMed, and Embase. Addressing the risk of colorectal cancer associated with mutations in the ERCC1 gene, no meta-analysis was conducted. Using Stata (version 12.0) applications, we effectively conducted a meta-analysis of thirteen case-control investigations and integrated the pooled odds ratios (ORs) according to a 95 % confidence interval (CI) of the overall and subgroup analysis.</div></div><div><h3>Results</h3><div>According to our findings, there appears to have been a noteworthy association found between rs3212986 and the risk of CRC in both the allele genetic model (OR 95 % CI = 1:44 (1.21–1.71) and the dominant genetic model (OR 95 % CI = 1:04 (0.93–1.15) for overall CRC.</div></div><div><h3>Conclusion</h3><div>In conclusion, the results of this meta-analysis showed that rs3212986 polymorphism was significantly associated with colorectal cancer risk, whereas rs11615 polymorphism was not significantly associated with colorectal cancer risk.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201361"},"PeriodicalIF":0.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Solute carrier family 2 (SLC2A) members have drawn interest in cancer research due to their crucial function in glucose metabolism. To understand their role in Head and Neck Squamous Cell Carcinoma (HNSCC), we have comprehensively analyzed the gene expression of SLC2A family members in HNSCC patients.
Method
RNAseq data of 520 HNSCC patients and 46 normals was downloaded from The Cancer Genome Atlas (TCGA) and analyzed using various statistical methods in R.
Result
Comparison of gene expression between normal and tumor samples showed significantly higher expression of SLC2A1, 4, 6, and 9 in tumor samples compared to normal. Further analysis revealed that both HPV(−)ve and HPV(+)ve samples showed significantly higher expression of SLC2A1 as compared to normal, though the difference was more pronounced in the case of HPV(−)ve. In contrast, SLC2A9 showed a highly significant difference between HPV(−)ve and normal but not between HPV(+)ve and normal. Furthermore, SLC2A genes showed significant variation among the basal (BA), classical (CL), and mesenchymal (MS) expression groups of HNSCC patients. SLC2A1 and 9 were significantly overexpressed in the BA group as compared to the other two groups, suggesting that these two genes can be utilized for the targeted therapy of HPV(−)ve HNSCC patients of the BA group.
Conclusion
Our results suggest that the biology of SLC2A family members is complex and, they may be playing different roles in different genomic backgrounds. More studies on SLC2A family members are needed to utilize them for targeted therapy or as diagnostic biomarkers.
{"title":"Solute carrier family 2 members (SLC2A) as potential targets for the treatment of head and neck squamous cell carcinoma patients","authors":"Anoop Kumar Tiwari , Devansh Jain , Sheikh Nizamuddin , Ravi Shanker Srivastava , Sanjay Singh , Sushant Kumar Shrivastava , Arun Khattri","doi":"10.1016/j.humgen.2024.201365","DOIUrl":"10.1016/j.humgen.2024.201365","url":null,"abstract":"<div><h3>Objective</h3><div>Solute carrier family 2 (SLC2A) members have drawn interest in cancer research due to their crucial function in glucose metabolism. To understand their role in Head and Neck Squamous Cell Carcinoma (HNSCC), we have comprehensively analyzed the gene expression of SLC2A family members in HNSCC patients.</div></div><div><h3>Method</h3><div>RNAseq data of 520 HNSCC patients and 46 normals was downloaded from The Cancer Genome Atlas (TCGA) and analyzed using various statistical methods in R.</div></div><div><h3>Result</h3><div>Comparison of gene expression between normal and tumor samples showed significantly higher expression of <em>SLC2A1</em>, <em>4, 6,</em> and <em>9</em> in tumor samples compared to normal. Further analysis revealed that both HPV(−)ve and HPV(+)ve samples showed significantly higher expression of <em>SLC2A1</em> as compared to normal, though the difference was more pronounced in the case of HPV(−)ve. In contrast, <em>SLC2A9</em> showed a highly significant difference between HPV(−)ve and normal but not between HPV(+)ve and normal. Furthermore, <em>SLC2A</em> genes showed significant variation among the basal (BA), classical (CL), and mesenchymal (MS) expression groups of HNSCC patients. <em>SLC2A1</em> and <em>9</em> were significantly overexpressed in the BA group as compared to the other two groups, suggesting that these two genes can be utilized for the targeted therapy of HPV(−)ve HNSCC patients of the BA group.</div></div><div><h3>Conclusion</h3><div>Our results suggest that the biology of SLC2A family members is complex and, they may be playing different roles in different genomic backgrounds. More studies on SLC2A family members are needed to utilize them for targeted therapy or as diagnostic biomarkers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201365"},"PeriodicalIF":0.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meta-analysis is a popular technique for aggregating evidence from a variety of similar studies for collective comparison. This paper presents data on genes and genetic variants (SNPs) associated with Type 2 Diabetes Mellitus, Diabetic Retinopathy, and Diabetic Nephropathy. Retinopathy and nephropathy are microvascular diseases that occur as a consequence of long-term diabetes. An overlap of the genes and SNPs revealed only one gene and one SNP to be common among the three diseases. The pathways associated with these diseases showed overlap to a certain extent. In this study, we have pooled all the genes and genetic variants associated with these three diseases and analyzed the overlaps/interactions. Such analyses lead to a better understanding of the disease mechanisms. We have analyzed the data using various tools such as KEGG, GO, and Network Analyst. Several genes were identified that have a significant role in the pathways of all three diseases. EPO is the only gene which was identified to be associated commonly among the three diseases. Among the genetic variants, rs1617640 of the gene EPO is the only common variant among the three diseases. The data cataloged in this paper serves as a genomic resource for diabetes and its associated microvascular diseases and it will also benefit as a resource for scientists working in this area of research.
元分析（Meta-analysis）是一种流行的技术，用于汇总来自各种类似研究的证据，以便进行集体比较。本文介绍了与 2 型糖尿病、糖尿病视网膜病变和糖尿病肾病相关的基因和遗传变异（SNPs）数据。视网膜病变和肾病是长期糖尿病导致的微血管疾病。基因和 SNP 的重叠显示，三种疾病中只有一个基因和一个 SNP 是共同的。与这些疾病相关的通路也有一定程度的重叠。在本研究中，我们汇集了与这三种疾病相关的所有基因和遗传变异，并对其重叠/相互作用进行了分析。这种分析有助于更好地了解疾病的机制。我们使用 KEGG、GO 和 Network Analyst 等多种工具对数据进行了分析。结果发现，有几个基因在这三种疾病的发病途径中都发挥了重要作用。EPO 是唯一一个被确定与三种疾病普遍相关的基因。在基因变异中，EPO 基因的 rs1617640 是三种疾病中唯一常见的变异。本文所收录的数据可作为糖尿病及其相关微血管疾病的基因组资源，也可作为从事该领域研究的科学家的资源。
{"title":"Meta-analysis of genes and genetic variants implicated in Type II diabetes mellitus, diabetic retinopathy, and diabetic nephropathy","authors":"A.N. Rizza , Nethra Lenin , Yazhini Ramaswamy , Deepak Kumar Sundaramoorthy , Rajiv Raman , Sinnakaruppan Mathavan","doi":"10.1016/j.humgen.2024.201362","DOIUrl":"10.1016/j.humgen.2024.201362","url":null,"abstract":"<div><div>Meta-analysis is a popular technique for aggregating evidence from a variety of similar studies for collective comparison. This paper presents data on genes and genetic variants (SNPs) associated with Type 2 Diabetes Mellitus, Diabetic Retinopathy, and Diabetic Nephropathy. Retinopathy and nephropathy are microvascular diseases that occur as a consequence of long-term diabetes. An overlap of the genes and SNPs revealed only one gene and one SNP to be common among the three diseases. The pathways associated with these diseases showed overlap to a certain extent. In this study, we have pooled all the genes and genetic variants associated with these three diseases and analyzed the overlaps/interactions. Such analyses lead to a better understanding of the disease mechanisms. We have analyzed the data using various tools such as KEGG, GO, and Network Analyst. Several genes were identified that have a significant role in the pathways of all three diseases. <em>EPO</em> is the only gene which was identified to be associated commonly among the three diseases. Among the genetic variants, rs1617640 of the gene <em>EPO</em> is the only common variant among the three diseases. The data cataloged in this paper serves as a genomic resource for diabetes and its associated microvascular diseases and it will also benefit as a resource for scientists working in this area of research.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201362"},"PeriodicalIF":0.5,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the present study network pharmacology analysis of AGK-2 and AK-7 (SIRT-2 inhibitors) were performed to elucidate their mechanism in regulating COPD pathogenesis.
Methods
Different database (Swiss Target Prediction, GeneCards and DisGeNet) were used for predicting targets of compound and disease. Drug-Target network was constructed using Cytoscape while functional enrichment and pathway analyses were performed using STRING database. ShinnyGo database was utilized for Annotation, Visualization, and Integrated Discovery, along with Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG). Molecular docking was performed to assess the binding affinities of AGK-2 and AK-7 to key proteins.
Results
AK-7 and AGK2 revealed 43 and 41 targets while 3392 targets related to COPD were found. Protein-protein interaction (PPI) network revealed 43 nodes and 133 edges for AK-7 and 41 nodes and 110 edges for AGK-2. Enrichment analysis highlighted distinct involvement of AGK-2 and AK-7 in various aspects of respiratory physiology including molecular signaling and neuronal secretions. AGK-2 revealed to influence pathways as EGFR and Ras/Raf/MAPK, while AK-7 targeted pathways like nitric oxide synthatase and tuberculosis, as well as regulating calcium signaling and neuro-immune interactions associated with COPD. Finally molecular docking revealed that AGK-2 showed good binding affinity with MAPK14 and STAT3. Whereas AK-7 with CASP3 and CXCL8. The findings highlight potency of AGK-2 and AK-7 in modulating inflammation, reactive oxygen species, and neuroimmune interactions, suggesting their efficacy in COPD management through SIRT-2 regulation.
Conclusion
The study offers novel insights into the potential of SIRT-2 inhibitors to modulate disease mechanisms at a molecular level.
{"title":"Network pharmacology and molecular docking insights into Sirtuin-2 inhibitors (AK-7 and AGK-2): A synergistic strategy for COPD treatment","authors":"Vandana Yadav , Vinita Pandey , Pratikkumar Gaglani , Atul Srivastava , Soni , Subhashini","doi":"10.1016/j.humgen.2024.201360","DOIUrl":"10.1016/j.humgen.2024.201360","url":null,"abstract":"<div><h3>Objective</h3><div>In the present study network pharmacology analysis of AGK-2 and AK-7 (SIRT-2 inhibitors) were performed to elucidate their mechanism in regulating COPD pathogenesis.</div></div><div><h3>Methods</h3><div>Different database (Swiss Target Prediction, GeneCards and DisGeNet) were used for predicting targets of compound and disease. Drug-Target network was constructed using Cytoscape while functional enrichment and pathway analyses were performed using STRING database. ShinnyGo database was utilized for Annotation, Visualization, and Integrated Discovery, along with Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG). Molecular docking was performed to assess the binding affinities of AGK-2 and AK-7 to key proteins.</div></div><div><h3>Results</h3><div>AK-7 and AGK2 revealed 43 and 41 targets while 3392 targets related to COPD were found. Protein-protein interaction (PPI) network revealed 43 nodes and 133 edges for AK-7 and 41 nodes and 110 edges for AGK-2. Enrichment analysis highlighted distinct involvement of AGK-2 and AK-7 in various aspects of respiratory physiology including molecular signaling and neuronal secretions. AGK-2 revealed to influence pathways as EGFR and Ras/Raf/MAPK, while AK-7 targeted pathways like nitric oxide synthatase and tuberculosis, as well as regulating calcium signaling and neuro-immune interactions associated with COPD. Finally molecular docking revealed that AGK-2 showed good binding affinity with MAPK14 and STAT3. Whereas AK-7 with CASP3 and CXCL8. The findings highlight potency of AGK-2 and AK-7 in modulating inflammation, reactive oxygen species, and neuroimmune interactions, suggesting their efficacy in COPD management through SIRT-2 regulation.</div></div><div><h3>Conclusion</h3><div>The study offers novel insights into the potential of SIRT-2 inhibitors to modulate disease mechanisms at a molecular level.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201360"},"PeriodicalIF":0.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.humgen.2024.201359
Menas A. Abdalla , Omer Alguily Yousif , Salah Eldin G. Elzaki , Ahmed Mohamedain , Hamdan Z. Hamdan
Background
Several reports have indicated the involvement of β2-adrenergic receptor gene (ADRB2) polymorphisms rs1042713 p.Gly16Arg and rs1042714 p.Glu27Gln in susceptibility to bronchial asthma and its clinical severity. This study investigated the genotype frequencies of these two polymorphisms in Sudanese patients with bronchial asthma, compared them to a healthy control group, and correlated the genotypes with the clinical severity of asthma.
Methods
A case-control study, matched for age, sex, and body mass index (BMI) was conducted at Al-Shaab Teaching Hospital in Khartoum, Sudan, between January and April 2022. The study included fifty subjects in each arm: adults with bronchial asthma were cases and healthy individuals were controls. Genotyping for rs1042713 p.Gly16Arg and rs1042714 p.Glu27Gln was determined by allele-specific polymerase chain reaction. Adjusted odds ratio (aOR) was calculated using asthma as a dependent factor and variables like ADRB2 gene polymorphisms, age, BMI, and sex as independent factor.
Results
The genotype GG (Gly16Gly) in the ADRB2 rs1042713 p.Gly16Arg was more prevalent in cases compared to controls (28 % vs. 10 %) and showed a significant risk effect for bronchial asthma [aOR = 3.81, 95 % CI (1.23–11.80); p = 0.020]. The allele G is more frequent in cases than controls, however it was not statistically significant [OR = 1.27, 95 % CI (0.72–2.22); p = 0.394]. For ADRB2 rs1042714 p.Glu27Gln, none of the genotypes or alleles showed any significant association with bronchial asthma. Additionally, none of the genotypes in the two gene polymorphisms were associated with the clinical severity of asthma.
Conclusion
In this study, the ADRB2 rs1042713 p.Gly16Arg gene polymorphism showed a significant risk effect for bronchial asthma, while no association was observed with ADRB2 rs1042714 p.Glu27Gln, further study is needed.
{"title":"β2_adrenergic receptor gene polymorphisms p.Gly16Arg and p. Glu27Gln in Sudanese patients with bronchial asthma: A case-control study","authors":"Menas A. Abdalla , Omer Alguily Yousif , Salah Eldin G. Elzaki , Ahmed Mohamedain , Hamdan Z. Hamdan","doi":"10.1016/j.humgen.2024.201359","DOIUrl":"10.1016/j.humgen.2024.201359","url":null,"abstract":"<div><h3>Background</h3><div>Several reports have indicated the involvement of β2-adrenergic receptor gene (ADRB2) polymorphisms rs1042713 p.Gly16Arg and rs1042714 p.Glu27Gln in susceptibility to bronchial asthma and its clinical severity. This study investigated the genotype frequencies of these two polymorphisms in Sudanese patients with bronchial asthma, compared them to a healthy control group, and correlated the genotypes with the clinical severity of asthma.</div></div><div><h3>Methods</h3><div>A case-control study, matched for age, sex, and body mass index (BMI) was conducted at Al-Shaab Teaching Hospital in Khartoum, Sudan, between January and April 2022. The study included fifty subjects in each arm: adults with bronchial asthma were cases and healthy individuals were controls. Genotyping for rs1042713 p.Gly16Arg and rs1042714 p.Glu27Gln was determined by allele-specific polymerase chain reaction. Adjusted odds ratio (aOR) was calculated using asthma as a dependent factor and variables like ADRB2 gene polymorphisms, age, BMI, and sex as independent factor.</div></div><div><h3>Results</h3><div>The genotype GG (Gly16Gly) in the <em>ADRB2</em> rs1042713 p.Gly16Arg was more prevalent in cases compared to controls (28 % vs. 10 %) and showed a significant risk effect for bronchial asthma [aOR = 3.81, 95 % CI (1.23–11.80); <em>p</em> = 0.020]. The allele G is more frequent in cases than controls, however it was not statistically significant [OR = 1.27, 95 % CI (0.72–2.22); <em>p</em> = 0.394]. For <em>ADRB2</em> rs1042714 p.Glu27Gln, none of the genotypes or alleles showed any significant association with bronchial asthma. Additionally, none of the genotypes in the two gene polymorphisms were associated with the clinical severity of asthma.</div></div><div><h3>Conclusion</h3><div>In this study, the <em>ADRB2</em> rs1042713 p.Gly16Arg gene polymorphism showed a significant risk effect for bronchial asthma, while no association was observed with <em>ADRB2</em> rs1042714 p.Glu27Gln, further study is needed.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201359"},"PeriodicalIF":0.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1016/j.humgen.2024.201357
Subhajit Ghosh, Ritobhas Datta, Subarna Thakur
Liver steatosis, also known as non-alcoholic fatty liver disease (NAFLD), is a condition marked by the buildup of fat in the liver. It is frequently linked to obesity, diabetes, and other risk factors such as hypertension, dyslipidemia, and a sedentary lifestyle. It has the potential to progress to non-alcoholic steatohepatitis (NASH), a condition characterized by liver inflammation and fibrosis. Without intervention, NASH can progress, eventually resulting in cirrhosis and, ultimately, hepatocellular carcinoma (HCC). Gaining a greater understanding of the molecular pathways that drive the progression of the disease could facilitate the development of more effective prognostic and monitoring tools. This study utilized a network-based methodology to do a meta-analysis on a large set of gene expression data from three studies, following the guidelines outlined by PRISMA. A study network was created, and differential gene expression (DGE) analysis was conducted to compare disease states. The common differentially expressed genes (DEGs) were identified, and mutual information network analysis unveiled associations among genes such as COL1A1, COL1A2, C8B, and AAMP across several stages. Further, GO and KEGG analyses identified 23 genes, and 21 pathways linked to fatty acid metabolism, inflammation, insulin signaling, cell cycle regulation, growth, apoptosis, and angiogenesis. Furthermore, the Gene Set Enrichment Analysis (GSEA) revealed that there were enriched transcriptional events in pathways such as Nucleotide Excision Repair, Type 2 Diabetes Mellitus, Cell Cycle, and Apoptosis. Nine prognostic genes, namely PGM2L1, ADA, INF2, COL1A1, RPL18A, SLC25A6, SLC39A7, TXN, and ALDH1A1, were identified using the Kaplan-Meier technique in survival analysis. The survival prediction probability was evaluated using regularization regression approaches- LASSO, Ridge, and Elastic-Net. The analysis of the tissue-specific expression data revealed notable expression of SLC39A7, SLC25A6, ALDH1A1, and INF2 in liver hepatocytes. The mutational data indicates alterations in the COL1A1, SLC39A1, INF2, RPL18A, and SLC25A6 genes in cases of hepatocellular carcinoma.
{"title":"Network-based meta-analysis of gene expression reveals novel prognostic biomarkers for the progression of hepatocellular carcinoma from non-alcoholic fatty liver disease","authors":"Subhajit Ghosh, Ritobhas Datta, Subarna Thakur","doi":"10.1016/j.humgen.2024.201357","DOIUrl":"10.1016/j.humgen.2024.201357","url":null,"abstract":"<div><div>Liver steatosis, also known as non-alcoholic fatty liver disease (NAFLD), is a condition marked by the buildup of fat in the liver. It is frequently linked to obesity, diabetes, and other risk factors such as hypertension, dyslipidemia, and a sedentary lifestyle. It has the potential to progress to non-alcoholic steatohepatitis (NASH), a condition characterized by liver inflammation and fibrosis. Without intervention, NASH can progress, eventually resulting in cirrhosis and, ultimately, hepatocellular carcinoma (HCC). Gaining a greater understanding of the molecular pathways that drive the progression of the disease could facilitate the development of more effective prognostic and monitoring tools. This study utilized a network-based methodology to do a meta-analysis on a large set of gene expression data from three studies, following the guidelines outlined by PRISMA. A study network was created, and differential gene expression (DGE) analysis was conducted to compare disease states. The common differentially expressed genes (DEGs) were identified, and mutual information network analysis unveiled associations among genes such as <em>COL1A1</em>, <em>COL1A2</em>, <em>C8B</em>, and <em>AAMP</em> across several stages. Further, GO and KEGG analyses identified 23 genes, and 21 pathways linked to fatty acid metabolism, inflammation, insulin signaling, cell cycle regulation, growth, apoptosis, and angiogenesis. Furthermore, the Gene Set Enrichment Analysis (GSEA) revealed that there were enriched transcriptional events in pathways such as Nucleotide Excision Repair, Type 2 Diabetes Mellitus, Cell Cycle, and Apoptosis. Nine prognostic genes, namely <em>PGM2L1</em>, <em>ADA</em>, <em>INF2</em>, <em>COL1A1</em>, <em>RPL18A</em>, <em>SLC25A6</em>, <em>SLC39A7</em>, <em>TXN</em>, and <em>ALDH1A1</em>, were identified using the Kaplan-Meier technique in survival analysis. The survival prediction probability was evaluated using regularization regression approaches- LASSO, Ridge, and Elastic-Net. The analysis of the tissue-specific expression data revealed notable expression of <em>SLC39A7</em>, <em>SLC25A6</em>, <em>ALDH1A1</em>, and <em>INF2</em> in liver hepatocytes. The mutational data indicates alterations in the <em>COL1A1</em>, <em>SLC39A1</em>, <em>INF2</em>, <em>RPL18A</em>, and <em>SLC25A6</em> genes in cases of hepatocellular carcinoma.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201357"},"PeriodicalIF":0.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esophageal Squamous Cell Carcinoma (ESCC) which is diagnosed in advanced stages and metastasis to the vital organs, remained the sixth fatal malignancy among other types of cancer-related death. Considering the lack of specific clinical symptoms in the early development of the disease, finding suitable biomarkers and tissue-specific alterations for effective screening of ESCC is targeted in this project. Gene expression profiles of tumor tissue and para-tumors of stage I ESCC patients were retrieved from the Gene Expression Omnibus (GEO) database. The significant tissue-specific differentially expressed genes (DEGs) were identified and studied based on fold change distribution and the functional role of genes in the action map. A total number of 11,483 significant DEGs discriminated the tumor tissue from para-tumor tissue. Clustering analysis of significant DEGs led to identifying 220 DEGs as the final significant genes. Protein interaction network and action map analysis of the final gene list showed matrix metallopeptidase-9 (MMP9) as the critical gene related to the development of ESCC diseases in stage I. Significant expression change of MMP9 in esophageal carcinoma was validated in UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal). This study highlighted the pivotal role of MMP9 in combination with SPP1, MMP13, and IL18 as a possible biomarkers panel in studies of tumor invasion and prognosis for stage I ESCC disease.
{"title":"Revealing key proteins in comparison of tumor and para-tumor tissues in stage I esophageal squamous cell carcinoma: A combined gene expression clustering and protein interaction network analysis","authors":"Maede Bakhshi Valilou , Mostafa Rezaei-Tavirani , Masoumeh Farahani","doi":"10.1016/j.humgen.2024.201355","DOIUrl":"10.1016/j.humgen.2024.201355","url":null,"abstract":"<div><div>Esophageal Squamous Cell Carcinoma (ESCC) which is diagnosed in advanced stages and metastasis to the vital organs, remained the sixth fatal malignancy among other types of cancer-related death. Considering the lack of specific clinical symptoms in the early development of the disease, finding suitable biomarkers and tissue-specific alterations for effective screening of ESCC is targeted in this project. Gene expression profiles of tumor tissue and para-tumors of stage I ESCC patients were retrieved from the Gene Expression Omnibus (GEO) database. The significant tissue-specific differentially expressed genes (DEGs) were identified and studied based on fold change distribution and the functional role of genes in the action map. A total number of 11,483 significant DEGs discriminated the tumor tissue from para-tumor tissue. Clustering analysis of significant DEGs led to identifying 220 DEGs as the final significant genes. Protein interaction network and action map analysis of the final gene list showed matrix metallopeptidase-9 (MMP9) as the critical gene related to the development of ESCC diseases in stage I. Significant expression change of MMP9 in esophageal carcinoma was validated in UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal). This study highlighted the pivotal role of MMP9 in combination with SPP1, MMP13, and IL18 as a possible biomarkers panel in studies of tumor invasion and prognosis for stage I ESCC disease.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201355"},"PeriodicalIF":0.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1016/j.humgen.2024.201356
Mohadeseh Khoshandam , Hossein Soltaninejad , Saman Hosseinkhani , Zohreh Saltanatpour , Mohammad Taghi Hedayati Goudarzi , Amir Ali Hamidieh
The CRISPR/Cas9 genome editing system is a unique and new technology that allows genetics and medical researchers to modify or edit parts of the genome. This is achieved by deleting, inserting, or changing parts of the DNA sequence. Currently, this method is considered the simplest, most widely used, and most accurate method of genetic manipulation. The system holds great potential for treating a wide range of genetic diseases. However, further research is necessary to determine the advantages and disadvantages of the CRISPR system and to establish best practices. On the other hand, individual patient treatment is a primary goal in the medical field. This goal has proven elusive due to a complex set of factors affecting disease and health. Recent advancements in enabling technologies that promote personalized and precision medicine are highlighted in this work. Artificial intelligence, which simulates human intelligence for computers, is utilized in the interface of machines programmed to think and behave like humans. This review article summarizes recent developments in the fields of artificial intelligence (AI) and CRISPR/Cas9, examining clinical trials and potential advancements in precision and personalized medicine, cancer treatment, and current/future challenges. Specifically, the application of AI in modifying the CRISPR/Cas9 system is emphasized.
CRISPR/Cas9 基因组编辑系统是一项独特的新技术，可让遗传学和医学研究人员修改或编辑基因组的某些部分。这是通过删除、插入或改变部分 DNA 序列来实现的。目前，这种方法被认为是最简单、应用最广泛、最准确的基因操作方法。该系统在治疗各种遗传疾病方面具有巨大潜力。然而，要确定 CRISPR 系统的优缺点并确立最佳做法，还需要进一步的研究。另一方面，个体化治疗病人是医学领域的首要目标。由于影响疾病和健康的因素错综复杂，这一目标一直难以实现。本文重点介绍了促进个性化和精准医疗的使能技术的最新进展。人工智能是为计算机模拟人类智能的技术，它被应用于机器的界面，通过编程，机器可以像人类一样思考和行为。这篇综述文章总结了人工智能（AI）和 CRISPR/Cas9 领域的最新发展，探讨了精准和个性化医疗、癌症治疗方面的临床试验和潜在进展，以及当前/未来的挑战。特别强调了人工智能在修改 CRISPR/Cas9 系统中的应用。
{"title":"CRISPR/Cas and artificial intelligence to improve precision medicine: Future perspectives and potential limitations","authors":"Mohadeseh Khoshandam , Hossein Soltaninejad , Saman Hosseinkhani , Zohreh Saltanatpour , Mohammad Taghi Hedayati Goudarzi , Amir Ali Hamidieh","doi":"10.1016/j.humgen.2024.201356","DOIUrl":"10.1016/j.humgen.2024.201356","url":null,"abstract":"<div><div>The CRISPR/Cas9 genome editing system is a unique and new technology that allows genetics and medical researchers to modify or edit parts of the genome. This is achieved by deleting, inserting, or changing parts of the DNA sequence. Currently, this method is considered the simplest, most widely used, and most accurate method of genetic manipulation. The system holds great potential for treating a wide range of genetic diseases. However, further research is necessary to determine the advantages and disadvantages of the CRISPR system and to establish best practices. On the other hand, individual patient treatment is a primary goal in the medical field. This goal has proven elusive due to a complex set of factors affecting disease and health. Recent advancements in enabling technologies that promote personalized and precision medicine are highlighted in this work. Artificial intelligence, which simulates human intelligence for computers, is utilized in the interface of machines programmed to think and behave like humans. This review article summarizes recent developments in the fields of artificial intelligence (AI) and CRISPR/Cas9, examining clinical trials and potential advancements in precision and personalized medicine, cancer treatment, and current/future challenges. Specifically, the application of AI in modifying the CRISPR/Cas9 system is emphasized.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201356"},"PeriodicalIF":0.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.humgen.2024.201354
Noor T. Kadhim, Abdul Kareem A. Alkazaz
Cluster of differentiation 244 (CD244), a member of the signaling lymphocytic activation molecule (SLAM) family, is one of the major cell surface receptors of the SLAM family with activating and inhibitory signaling potentials that is involved in the functional regulation of inflammatory reactions. It has recently been suggested that soluble CD244 levels are dysregulated in patients with rheumatoid arthritis (RA), but the evidence is not conclusive. Furthermore, the CD244 rs3766379 variant showed conflicting results regarding association with disease susceptibility. In this cross-sectional case-control study, serum CD244 concentration was determined in 123 RA patients and 60 controls using an enzyme-linked immunosorbent assay kit. The CD244 rs3766379 variant was also genotyped using real-time polymerase chain reaction principles. Results revealed that Log10-transformed serum concentrations (mean ± standard error) of soluble CD244 were significantly elevated in RA patients compared to controls (0.53 ± 0.04 vs. 0.29 ± 0.02 ng/mL; probability = 0.003), especially in patients with high disease activity (0.73 ± 0.12 vs. 0.29 ± 0.02 ng/mL; probability = 0.003), where CD244 showed reliable discrimination between patients and controls (area under the curve = 0.698; probability = 0.023). The rs3766379 allele and genotype frequencies showed no significant differences between patients and controls. Furthermore, this variant did not affect CD244 concentration. In conclusion, CD244 levels were up-regulated in the serum of patients with RA, particularly those with high disease activity. The CD244 rs3766379 variant was not associated with susceptibility to RA and had no effect on serum CD244 concentration.
{"title":"The CD244 rs3766379 variant showed no association with susceptibility to rheumatoid arthritis while soluble CD244 was associated with disease activity","authors":"Noor T. Kadhim, Abdul Kareem A. Alkazaz","doi":"10.1016/j.humgen.2024.201354","DOIUrl":"10.1016/j.humgen.2024.201354","url":null,"abstract":"<div><div>Cluster of differentiation 244 (CD244), a member of the signaling lymphocytic activation molecule (SLAM) family, is one of the major cell surface receptors of the SLAM family with activating and inhibitory signaling potentials that is involved in the functional regulation of inflammatory reactions. It has recently been suggested that soluble CD244 levels are dysregulated in patients with rheumatoid arthritis (RA), but the evidence is not conclusive. Furthermore, the <em>CD244</em> rs3766379 variant showed conflicting results regarding association with disease susceptibility. In this cross-sectional case-control study, serum CD244 concentration was determined in 123 RA patients and 60 controls using an enzyme-linked immunosorbent assay kit. The <em>CD244</em> rs3766379 variant was also genotyped using real-time polymerase chain reaction principles. Results revealed that Log<sub>10</sub>-transformed serum concentrations (mean ± standard error) of soluble CD244 were significantly elevated in RA patients compared to controls (0.53 ± 0.04 vs. 0.29 ± 0.02 ng/mL; probability = 0.003), especially in patients with high disease activity (0.73 ± 0.12 vs. 0.29 ± 0.02 ng/mL; probability = 0.003), where CD244 showed reliable discrimination between patients and controls (area under the curve = 0.698; probability = 0.023). The rs3766379 allele and genotype frequencies showed no significant differences between patients and controls. Furthermore, this variant did not affect CD244 concentration. In conclusion, CD244 levels were up-regulated in the serum of patients with RA, particularly those with high disease activity. The <em>CD244</em> rs3766379 variant was not associated with susceptibility to RA and had no effect on serum CD244 concentration.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201354"},"PeriodicalIF":0.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.humgen.2024.201351
Subhadip Das, Debarghya Bhattacharyya, Md. Arshad, Chittabrata Mal
Background
The innate immune response, crucial for detecting microbial threats, relies on pattern recognition receptors like NLRC4 (NOD-like receptor family CARD domain-containing protein 4). NLRC4 triggers inflammasome assembly upon detecting bacterial flagellin and needle protein, releasing pro-inflammatory cytokines. Recent research emphasizes NLRC4 inflammasomes' role in malignancies, indicating their impact on cancer progression and immune regulation.
Methods
To comprehensively investigate the genetic variability, therapeutic implications, and biological relevance of NLRC4 across human cancers, we conducted a pan-cancer analysis utilizing diverse bioinformatics tools including different omics data. These tools included GEPIA, Kaplan-Meier Plotter, cBioPortal, TIMER2.0, Enrichr, Human Protein Atlas, IID, MuTarget Analysis, MAGIC, TargetScan, and CTD. Our analysis aimed to elucidate NLRC4 expression patterns, survival outcomes, pathway enrichment, regulatory mechanisms, and associations with genetic alterations and immune infiltration in various cancer subtypes.
Results
Our findings revealed a widespread upregulation of NLRC4 expression in 19 out of 31 major human cancer subtypes, with significant correlations observed with overall survival (OS) in SARC and THCA, and relapse-free survival (RFS) in HNSC, KIRP, and PAAD. Enrichment analyses identified intricate connections between NLRC4-associated genes and diverse biological pathways. Additionally, miRNAs, hub genes, and transcription factors regulating NLRC4 emerged as key players in cancer pathogenesis.
Conclusions
Our study highlights NLRC4's potential as a pan-cancer biomarker and therapy focus in human cancers. Associations with survival outcomes, pathways, and regulatory networks illuminate NLRC4's multifaceted cancer role, urging a deeper investigation into its mechanisms and therapeutic potential for patient benefit.
{"title":"The potential of the NLRC4 Inflammasome as a Cancer biomarker: A Pan-cancer investigation","authors":"Subhadip Das, Debarghya Bhattacharyya, Md. Arshad, Chittabrata Mal","doi":"10.1016/j.humgen.2024.201351","DOIUrl":"10.1016/j.humgen.2024.201351","url":null,"abstract":"<div><h3>Background</h3><div>The innate immune response, crucial for detecting microbial threats, relies on pattern recognition receptors like NLRC4 (NOD-like receptor family CARD domain-containing protein 4). NLRC4 triggers inflammasome assembly upon detecting bacterial flagellin and needle protein, releasing pro-inflammatory cytokines. Recent research emphasizes NLRC4 inflammasomes' role in malignancies, indicating their impact on cancer progression and immune regulation.</div></div><div><h3>Methods</h3><div>To comprehensively investigate the genetic variability, therapeutic implications, and biological relevance of NLRC4 across human cancers, we conducted a pan-cancer analysis utilizing diverse bioinformatics tools including different omics data. These tools included GEPIA, Kaplan-Meier Plotter, cBioPortal, TIMER2.0, Enrichr, Human Protein Atlas, IID, MuTarget Analysis, MAGIC, TargetScan, and CTD. Our analysis aimed to elucidate NLRC4 expression patterns, survival outcomes, pathway enrichment, regulatory mechanisms, and associations with genetic alterations and immune infiltration in various cancer subtypes.</div></div><div><h3>Results</h3><div>Our findings revealed a widespread upregulation of NLRC4 expression in 19 out of 31 major human cancer subtypes, with significant correlations observed with overall survival (OS) in SARC and THCA, and relapse-free survival (RFS) in HNSC, KIRP, and PAAD. Enrichment analyses identified intricate connections between NLRC4-associated genes and diverse biological pathways. Additionally, miRNAs, hub genes, and transcription factors regulating NLRC4 emerged as key players in cancer pathogenesis.</div></div><div><h3>Conclusions</h3><div>Our study highlights NLRC4's potential as a pan-cancer biomarker and therapy focus in human cancers. Associations with survival outcomes, pathways, and regulatory networks illuminate NLRC4's multifaceted cancer role, urging a deeper investigation into its mechanisms and therapeutic potential for patient benefit.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201351"},"PeriodicalIF":0.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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