Human Gene最新文献

{"title":"KRT14 as a potential prognostic marker for metastasis in metaplastic breast carcinoma","authors":"Bhaskar Gogoi ,&nbsp;Benjamin Lalrinpuia ,&nbsp;Lalhmingliana ,&nbsp;Nachimuthu Senthil Kumar","doi":"10.1016/j.humgen.2024.201341","DOIUrl":"10.1016/j.humgen.2024.201341","url":null,"abstract":"<div><div>Metaplastic breast cancer (MBC) is an aggressive breast cancer subtype with poor prognosis. To elucidate underlying genomic aberrations driving MBC, we conducted integrated transcriptomic analyses of MBC tumors and basal breast cancer cell lines with various transitioning phases (xE = epithelial phase clone, xM = mesenchymal phase clone and xEM = Epithelial-mesenchymal clone). Differential gene expression analysis between MBC vs non-MBC samples as well as between epithelial-mesenchymal (xEM) transitioning cells vs parental cells revealed 12 commonly dysregulated genes intersected from both the datasets meditates pathways governing EMT, migration, proliferation and metastasis. Further investigation onto those genes based on multi-omics approaches that include survival analysis, correlated expression patterns and interactomics indicated KRT14 had a key role in promoting MBC aggression through Epithelial mesenchymal transition leading to metastasis. Moreover, NPR3 was found to be a possible link between KRT14 and EMT in metastasis. To our knowledge, this is the first evident gene expression study to investigate the potential association between the expression of KRT14 and NPR3 and metastasis in MBC, and their potential involvement in the epithelial-mesenchymal transition (EMT) process. These mechanistic and prognostic insights gained can lead to targeted therapeutics against this rare, refractory disease. Overall, this work highlights the effectiveness of integrated multi-omics in revealing gene expression pattern and predictive biomarkers for metaplastic breast cancer subtypes with poor prognosis.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201341"},"PeriodicalIF":0.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418244","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}

{"title":"Therapeutic prospects and challenges in the human genetic disorder hyperbiliverdinemia","authors":"Sakshi Singh ,&nbsp;Manish Dwivedi ,&nbsp;Aiswarya Pawar ,&nbsp;Mahima Kori ,&nbsp;Anuradha Yadav ,&nbsp;Paras Porwal","doi":"10.1016/j.humgen.2024.201342","DOIUrl":"10.1016/j.humgen.2024.201342","url":null,"abstract":"<div><div>The epidermis, sclera, urine, and other bodily fluids have a greenish tint in hyperbiliverdinemia, a rare hepatic condition. Increased biliverdin as a result of ineffective conversion to bilirubin is the known explanation behind the onset of this disorder. The conversion of the bile pigment biliverdin to bilirubin is catalyzed by the oxidoreductase enzyme biliverdin reductase IX-α. Based on a case study, the development of hyperbiliverdinemia is reportedly caused by a novel mutation in the gene (BVRA) that encodes the protein biliverdin reductase A (enzyme) paired with a decompensated liver. Those who have been affected do not seem to experience symptoms outside of obstructive cholestasis; sometimes it is accompanied by liver failure; however, in some reports, liver failure is the only symptom faced by the affected individual. According to case reports, green jaundice occasionally goes away once obstructive cholestasis becomes resolved. This review examines jaundice, including its etiology, symptoms, and concomitant disease processes, with a focus on hyperbiliverdinemia, popularly known as “green jaundice.” Significant information regarding the therapeutics and treatment of jaundice, such as that of phototherapy and exchange transfusion, has also been discussed. Currently, there is no specific treatment for hyperbiliverdinemia; however, treating the symptoms of this disease seems to improve the affected individual's condition.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201342"},"PeriodicalIF":0.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418245","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}

{"title":"Investigation of the association between polymorphisms in DNA repair enzymes and STEMI","authors":"Damla Raimoglou ,&nbsp;Murat Cimci ,&nbsp;Elif Citak ,&nbsp;Selin Unal ,&nbsp;Narmina Malikova ,&nbsp;Eser Durmaz ,&nbsp;Mehmet Guven","doi":"10.1016/j.humgen.2024.201340","DOIUrl":"10.1016/j.humgen.2024.201340","url":null,"abstract":"<div><div>STEMI (ST-elevation myocardial infarction), a condition in which DNA damage likely contributes to its pathogenesis, is among the most severe manifestations of coronary artery disease. There are very few publications in this field in the literature. In our study, we examined the association between four polymorphisms in repair enzymes (<em>LIG4 Thr9Ile</em>, <em>XRCC6 promoter C-57G</em>, <em>XPA -4A/G</em>, <em>OGG1 Ser326Cys</em>) involved in three distinct DNA repair mechanisms [NHEJ (non-homologous end joining)], NER (nucleotide excision repair), and BER (base excision repair), and their impact on the risk of STEMI. This study involved 185 patients diagnosed with STEMI and included 155 healthy controls. The genotyping of SNPs was conducted through the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) method for the following variants: <em>XRCC6</em> (rs2267437), <em>XPA</em> (rs1800975), <em>LIG4 (</em>rs1805388), and <em>OGG1</em> (rs1052133). No significant differences were observed in the genotype distributions of the <em>XRCC6</em> and <em>OGG1</em> variations between the control and patient groups. On the other hand, our findings indicate that individuals carrying the mutant <em>G</em> allele for <em>XPA</em> polymorphism and the mutant <em>T</em> allele for <em>LIG4</em> polymorphism are susceptible to STEMI. Our findings demonstrate the significance of NHEJ and NER DNA repair processes in the pathogenesis of STEMI, as evidenced by the observed relationship between <em>LIG4</em> and <em>XPA</em> polymorphisms.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201340"},"PeriodicalIF":0.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318694","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}

{"title":"Altered expression of insulin-like growth factor 2 mRNA binding protein 2 is associated with periodontal disease- a case-control analysis","authors":"Deepika Burra Anand ,&nbsp;Jaiganesh Ramamurthy ,&nbsp;Balachander Kannan ,&nbsp;Vijayashree Priyadharsini Jayaseelan ,&nbsp;Paramasivam Arumugam","doi":"10.1016/j.humgen.2024.201338","DOIUrl":"10.1016/j.humgen.2024.201338","url":null,"abstract":"<div><h3>Background/Purpose</h3><p>Periodontitis has a multifactorial pathogenesis involving genetic and epigenetic factors. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an N6-methyladenosine (m6A) reader that enhances messenger RNA (mRNA) stability in an m6A-dependent manner. It is being considered as a potential target for treating inflammatory diseases. However, its role in periodontitis and its specific target genes affected by m6A modification are not yet well understood. This study aims to investigate the expression of IGF2BP2 and its potential involvement in periodontitis.</p></div><div><h3>Materials and methods</h3><p>Seventy participants were recruited, including 35 patients with periodontitis and 35 healthy controls. Clinical examination and radiography were performed to confirm a diagnosis of periodontitis. Gingival tissue samples were collected from each participant, and IGF2BP2 expression was measured using real-time PCR and western blotting. In addition, <em>in silico</em> tools were used to identify the IGF2BP2 network pathway and its functions.</p></div><div><h3>Results</h3><p>IGF2BP2 expression was significantly higher in the periodontitis group than in the healthy control group (<em>p</em> &lt; 0.0001). Functional enrichment analysis revealed that the IGF2BP2 pathway network plays a crucial role in periodontal pathogenesis. In addition, pro-inflammatory cytokines, including <em>IL-1β</em> and <em>IL-6</em>, were significantly increased in the periodontitis group (<em>p</em> &lt; 0.0001) and were positively correlated with IGF2BP2 expression and m6A methylation sites.</p></div><div><h3>Conclusion</h3><p>Our study demonstrated that increased IGF2BP2 expression is associated with periodontitis, which may regulate proinflammatory cytokine production in an m6A-dependent manner. Further functional studies are required to understand the mechanism of action of IGF2BP2 in periodontitis.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201338"},"PeriodicalIF":0.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272947","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}

{"title":"Role of GSTP1 functional polymorphisms in molecular pathogenesis of colorectal cancer","authors":"Sravanthi Malempati ,&nbsp;Neelam Agrawal ,&nbsp;Devalaraju Ravisankar ,&nbsp;Venkata Sai Rahul Trivedi Kothapalli ,&nbsp;Srinivasulu Cheemanapalli ,&nbsp;Raghava Rao Tamanam ,&nbsp;Suresh Govatati ,&nbsp;Pasupuleti Sreenivasa Rao","doi":"10.1016/j.humgen.2024.201335","DOIUrl":"10.1016/j.humgen.2024.201335","url":null,"abstract":"<div><p>Glutathione S-transferase P1 (GSTP1) plays a crucial role in the detoxification of harmful substances and cancer-causing agents. Single nucleotide polymorphisms (SNPs) in GSTP1 can affect its ability to catalyze reactions and detoxify, thereby influencing the risk of developing colorectal cancer (CRC). This study aimed to investigate the impact of functional SNPs (fSNPs) in GSTP1 on the risk of CRC, as well as their structural and functional consequences. We analyzed a total of 126 selected GSTP1 SNPs, including fSNPs <em>rs1695 A &gt; G</em> (I105V) and <em>rs1138272 C &gt; T</em> (A114V), in CRC patients (<em>n</em> = 103) and controls (<em>n</em> = 107) of south Indian origin using PCR-sequencing analysis with genomic DNA from blood samples. To assess the structural integrity of <em>GSTP1</em> fSNPs, we conducted in silico analysis using various tools such as Swiss PDB Viewer, pyMOL mutagenesis wizard, ProSA-Web, and Pdbsum. Additionally, we performed functional characterization of <em>GSTP1</em> fSNPs using cell and molecular biology techniques. Our findings revealed a significant association between the I105V fSNP and CRC risk, while the A114V fSNP did not show any significance. However, both fSNPs exhibited stronger linkage disequilibrium in patients compared to controls. In silico analysis indicated a loss of structural integrity and reduced electrostatic potential energy in the double mutant <em>GSTP1</em> (V105/V114) compared to the native (I105/A114) or single mutant (V105/A114 and I105/V114) forms. Furthermore, FHC cells transfected with the <em>GSTP1</em> I105V variant exhibited increased proliferation, invasion, and colony formation, along with decreased GST activity compared to carriers of the wild-type <em>GSTP1</em>. On the other hand, the <em>GSTP1</em> A114V variant did not show a significant effect. Interestingly, FHC cells transfected with the double mutant <em>GSTP1</em> variant (V105/V114) demonstrated synergistic and enhanced effects compared to the <em>GSTP1</em> I105V variant. Consistent with these findings, plasma GST activity was significantly lower in haplogroups carrying both fSNPs compared to haplogroups with single or no fSNPs. To summarize, our findings indicate that while <em>GSTP1</em> I105V alone contributes to the etiology of CRC, A114V does not; however, their combined presence has a more significant impact.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201335"},"PeriodicalIF":0.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232621","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}

{"title":"Impact of family dynamics on cancer progression and patient outcomes: An analysis of emotional and psychological support","authors":"Hashim Talib Hashim ,&nbsp;Ali Talib Hashim ,&nbsp;Ali Mahdi Mansour ,&nbsp;Hossam Tharwat Ali ,&nbsp;Narjiss Aji ,&nbsp;Maryam Chichah ,&nbsp;Mrinmoy Kundu ,&nbsp;Amasee Falah Jabbar","doi":"10.1016/j.humgen.2024.201339","DOIUrl":"10.1016/j.humgen.2024.201339","url":null,"abstract":"<div><h3>Background</h3><p>Cancer is a group of diseases that results from the growth of cells in an uncontrolled way, and in addition spreading of abnormal cells. At the molecular level, Alterations of oncogenes, tumor-suppresser genes, and microRNA genes cause cancer. These alterations of genes usually occur at the somatic level, if they occur as germline mutations, they can cause heritable or familial cancer.</p></div><div><h3>Materials/methods</h3><p>This is a cross-sectional study which aims to find if there is any relationship between genetic relationship (genes) and cancer development, symptoms severity and prognosis. This study was conducted during the period of January 2022 and August 2022, and consisted of 1998 participants.</p></div><div><h3>Results</h3><p>There was a statistical difference in the distribution of participants' relative symptoms severity and improvement based on the duration they stayed with those people. Staying for days followed by weeks was the most reported in the group of participants with the same symptoms' severity of the diseased relative. On the opposite side, a longer duration of years was the predominant for worse symptoms of the family members despite the improvement of the patient.</p></div><div><h3>Conclusions</h3><p>Family history of cancer has been used by epidemiologists as a proxy for a genetically determined predisposition. However, a shared environment and similar lifestyles can also lead to multiple cancers in the same family. Genes' communication has a role in spreading the cancer among families.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201339"},"PeriodicalIF":0.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239926","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}

{"title":"Serum oxidative stressors levels and association of mtDNA variants with type 2 diabetes mellitus in the Central India population","authors":"Tejas Tajane ,&nbsp;Prafulla Ambulkar ,&nbsp;Pranita Waghmare ,&nbsp;Bharati Taksande ,&nbsp;Jwalant Waghmare","doi":"10.1016/j.humgen.2024.201337","DOIUrl":"10.1016/j.humgen.2024.201337","url":null,"abstract":"<div><h3>Background</h3><p>The mitochondrial genome has a high rate of mutability which plays a major role in pathogenic mutations. These mutations are implicated with mitochondrial dysfunction increasing the vulnerability to Diabetes Mellitus (DM).</p></div><div><h3>Aim</h3><p>The study aimed to evaluate the changes in oxidative markers and analyse the specific mitochondrial DNA variants that contributed to DM in the central Indian population.</p></div><div><h3>Method</h3><p>To assess mitogenomic alteration, Sanger sequencing was used to identify the single nucleotide polymorphisms (SNPs) or variants, while ELISA kits were used to evaluate oxidative stress.</p></div><div><h3>Results</h3><p>The levels of 8-Hydroxy-2-deoxyguanosine (8-OHdG) and Malondialdehyde (MDA) in type 2 diabetes mellitus (T2DM) were significantly higher than in healthy individual (HI). In T2DM (3371.80 ± 1110.7 pg/ml) the levels of 8-OHdG were significantly greater and were found to be nine times higher compared to the control group (<em>P</em> &lt; 0.001). Additionally, MDA level which is indicative of lipid peroxidation, in the diabetic groups (39.34 ± 23.05 ng/ml) contributed to 18 times higher than the control groups (2.16 ± 2 ng/ml). Moreover, 52 variants were found in our population, among which C10400T variants were significantly prevalent and clustered with the A10398G. These variants confirmed a strong association, on analysis for linkage disequilibrium (r²), with a slightly higher r² value in the T2DM group (0.92) compared to controls (0.85), indicating a stronger link with diabetes. According to multivariate regression analysis, variants associated with the mitogenome such as C16192T (CI: 0.004 to 1.30, <em>p</em> = 0.028) were found to play a protective role against T2DM. Furthermore, A3384G and G16129A may contribute to the protective role against the risk of developing diabetes.</p></div><div><h3>Conclusion</h3><p>The study demonstrates that diabetic patients are more vulnerable to certain mtDNA variants, directly linked to increased hyperglycemia. Elevated free radical-mediated oxidative stress likely affects these mtDNA variants.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201337"},"PeriodicalIF":0.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229784","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}

{"title":"Minning of Immuno-mitotic and GABAergic genes as potential biomarkers of glioblastoma: An integrated transcriptomic analysis","authors":"Naureen Mallick,&nbsp;Reaz Uddin","doi":"10.1016/j.humgen.2024.201336","DOIUrl":"10.1016/j.humgen.2024.201336","url":null,"abstract":"<div><p>Glioblastoma (GBM) is a highly lethal Central Nervous System (CNS) tumor prevalent in both adults and children, exhibiting elevated rates of mortality and morbidity. Due to the heterogenous nature of GBM, coupled with its nonspecific symptoms underscore the imperative for innovative biomarkers to enhance prognosis and the development of efficacious therapeutic interventions. This bioinformatics study seeks to elucidate the culprit genes, both up-regulated and down-regulated, within the context of their functional relevance, through a comparative analysis of gene expression profiles in GBM and normal brain tissues. Deregulated genes were identified from two Gene Expression Omnibus (GEO) datasets, employing the GEO2R tool to analyze expression data from normal and GBM tissues. Subsequently, differences in expression of genes (DEGs) through functional enrichment analysis were conducted by DAVID to discern their functional implications. Further, Protein-Protein Interaction (PPI) networks were constructed to identify hub genes among the selected up-regulated and down-regulated genes, employing various bioinformatics tools. The impact of the selected hub genes on patient overall survival was investigated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Notably, the up-regulated hub genes KIF2C and TTK exhibited significant correlations with overall survival, implicating their potential as immuno-mitotic biomarkers. Conversely, GAD2, the sole down-regulated hub gene, emerged as a promising molecular target for GBM, given its association with GABAergic signaling and amino acid metabolism. Consequently, these findings suggest that KIF2C and TTK may serve as immune-mitotic biomarkers, while GAD2 could be explored as a molecular target for GBM therapy. Nevertheless, additional research is essential to unravel the precise mechanistic underpinnings of GBM.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201336"},"PeriodicalIF":0.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229786","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}

{"title":"Liquid biopsy in brain tumors: Potential for impactful clinical applications","authors":"Tania Eid ,&nbsp;Lina Ghandour ,&nbsp;Joseph Abi Ghanem ,&nbsp;Hazem Assi ,&nbsp;Rami Mahfouz","doi":"10.1016/j.humgen.2024.201333","DOIUrl":"10.1016/j.humgen.2024.201333","url":null,"abstract":"<div><p>Despite the improvements in diagnostic and therapeutic techniques, heterogeneous constitution and non-invasive diagnosis remain major clinical challenges for brain tumors. In such a context, liquid biopsy is a noninvasive method that analyses tumor-derived biomarkers in body fluids and thus appears quite promising. This review explores the potential for circulating tumor cells, circulating tumor DNA, microRNAs, proteins, and exosomes as liquid biopsy markers in brain tumors. Although such biomarkers have potential for early detection, monitoring of disease progression, and guiding therapy, the limitations in the form of low levels of biomarkers and analytical complexities persist. Artificial intelligence integrated with liquid biopsy can therefore be expected to improve diagnostic accuracy and clinical utility. Further research, standardization, and clinical validation are needed to exploit the full potential of liquid biopsy in brain tumor management.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201333"},"PeriodicalIF":0.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773044124000779/pdfft?md5=a38488b52d1ae0ec4f9454b7d9fb5e75&pid=1-s2.0-S2773044124000779-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of mutational features of colorectal cancer and multiple primary cancers including colorectal component: Data from the Cancer Genome Atlas","authors":"Nataliya N. Timoshkina,&nbsp;Dmitry Yu Gvaldin,&nbsp;Moez Eid,&nbsp;Dema Alset,&nbsp;Nataliya A. Petrusenko,&nbsp;Inna A. Novikova,&nbsp;Oleg I. Kit","doi":"10.1016/j.humgen.2024.201334","DOIUrl":"10.1016/j.humgen.2024.201334","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is the second in mortality among cancers with high incidence worldwide. About 5 % of patients had a previous oncopathology and 20 % develop a second malignancy. CRC molecular genetic mechanisms in primary multiple cancers (MPCs) are not fully understood. This study aimed to investigate mutational characteristics of primary CRC compared to MPCs with colorectal component. 336 CRC patients and 52 MPCs patients with a colorectal component (C97CRC) (TCGA-COAD data) were included. Comparative bioinformatics analysis of genetic mutations, their interactions, effect on signaling pathways, survival rate, and druggable categories was conducted. CRC was characterized by <em>PIK3CA</em> and <em>APC</em> mutations, while 17 mutations in other genes were identified in C97CRC. In CRC group, co-occurring somatic variants in <em>TP53/APC</em> and <em>KRAS/APC</em> were the most common, while in C97CRC, <em>KRAS/SOX9</em> was specifically found. <em>TP53</em>/<em>SYNE1</em>, <em>TP53</em>/<em>MUC16</em>, and <em>TP53/TTN</em> mutational combinations were associated with a decreased survival rate in CRC group. Collagen type VI α3-chain protease and its inhibitor were suggested as specific druggable targets in C97CRC group. The differences in mutational profiles between groups may indicate evolutionary features of CRC as a primary and secondary malignancy. Described druggable categories open up prospects for treatment development of CRC and MPCs with a colorectal component.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201334"},"PeriodicalIF":0.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150724","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}