Pharmacogenomics & Personalized Medicine最新文献

{"title":"A Review of the Pharmacokinetic Characteristics of Immune Checkpoint Inhibitors and Their Clinical Impact Factors.","authors":"Jun-Chen Liu,&nbsp;Hong-Jing Yu","doi":"10.2147/PGPM.S391756","DOIUrl":"https://doi.org/10.2147/PGPM.S391756","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have been shown to be significant in improving the overall survival rate in certain malignancies with poor prognoses. However, only 20-40% of patients achieve long-term benefits, highlighting the relevance of the factors that influence the treatment, which can help clinicians improve their results and guide the development of new immune checkpoint therapies. In this study, the current pharmacokinetic aspects associated with the ICIs and the factors influencing clinical efficacy were characterised, including in terms of drug metabolism, drug clearance, hormonal effects and immunosuppressive effects.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"29-36"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/44/pgpm-16-29.PMC9880024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10591018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rs11479 in <i>Thymidine Phosphorylase</i> Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.","authors":"Xiongjie Jia,&nbsp;Tao Zhang,&nbsp;Junjie Sun,&nbsp;Hengxue Lin,&nbsp;Tianliang Bai,&nbsp;Yating Qiao,&nbsp;Yaxin Li,&nbsp;Gang Li,&nbsp;Guicun Li,&nbsp;Xinyu Peng,&nbsp;Aimin Zhang","doi":"10.2147/PGPM.S397382","DOIUrl":"https://doi.org/10.2147/PGPM.S397382","url":null,"abstract":"<p><strong>Objective: </strong><i>Thymidine Phosphorylase (TYMP)</i> gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between <i>TYMP</i> polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy.</p><p><strong>Methods: </strong>A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of <i>TYMP</i> polymorphism and <i>TYMP</i> mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of <i>TYMP</i> according to genotype status was analyzed using non-parameter test.</p><p><strong>Results: </strong>Prevalence of rs11479 in <i>TYMP</i> among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (<i>P</i>=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (<i>P</i>=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (<i>P</i>=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, <i>P</i>=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of <i>TYMP</i> than that of patients with GG genotype (<i>P</i><0.001).</p><p><strong>Conclusion: </strong>Polymorphism rs11479 in <i>TYMP</i> gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of <i>TYMP</i>. The conclusion of this study should be validated in prospective clinical trials subsequently.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"277-289"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/d2/pgpm-16-277.PMC10072144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9260035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Myeloid Leukemia Secondary to Chronic Lymphocytic Leukemia After Prolonged Chlorambucil Therapy: A Case Report.","authors":"Yan Wu,&nbsp;Shan Liu,&nbsp;Dongmei Wang,&nbsp;Xinjie Yao","doi":"10.2147/PGPM.S407940","DOIUrl":"https://doi.org/10.2147/PGPM.S407940","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to improve the understanding of acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL), and to explore the sequence of occurrence and clonal origin of the two diseases.</p><p><strong>Case report: </strong>We reported a case of a 71-year-old man with a history of CLL. The patient was administrated with chlorambucil for 19 years and was admitted to our hospital due to fever. Then he was subjected with routine blood tests, bone marrow smear examination, flow cytometric immunophenotyping and cytogenetic analysis. A final diagnosis of AML-M2 secondary to CLL with -Y,del(4q),del(5q),-7,add(12p),der(17),der(18),-22,+mar was made. After rejecting the therapy with Azacitidine combined with B-cell lymphoma-2 (Bcl-2) inhibitor, the patient died of pulmonary infection.</p><p><strong>Conclusion: </strong>This case highlights the rare occurrence of AML secondary to CLL after prolonged chlorambucil therapy and the poor prognosis of such cases, underscoring the importance of enhanced assessment of these patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"401-405"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/7e/pgpm-16-401.PMC10150764.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9416257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of Novel Pathogenic Variants in Two Families with Recurrent Fetal Congenital Heart Defects.","authors":"Rongqin Cai,&nbsp;Ya Tan,&nbsp;Mingming Wang,&nbsp;Huijun Yu,&nbsp;Jing Wang,&nbsp;Zhuo Ren,&nbsp;Zhe Dong,&nbsp;Yiwen He,&nbsp;Zhi Li,&nbsp;Li Lin,&nbsp;Ying Gu","doi":"10.2147/PGPM.S394120","DOIUrl":"https://doi.org/10.2147/PGPM.S394120","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing.</p><p><strong>Results: </strong>In family A, a compound heterozygous variation in <i>PLD1</i> gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant <i>ZIC3</i>: c.861delG (p.G289Afs*119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants <i>PLD1</i>: c.1132dupA and <i>ZIC3</i>: c.861delG were novel.</p><p><strong>Conclusion: </strong>The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"173-181"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/42/pgpm-16-173.PMC10008912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9475734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study.","authors":"Zhifei Hou,&nbsp;Xinran Zhang,&nbsp;Yong Gao,&nbsp;Jing Geng,&nbsp;Yu Jiang,&nbsp;Huaping Dai,&nbsp;Chen Wang","doi":"10.2147/PGPM.S409644","DOIUrl":"https://doi.org/10.2147/PGPM.S409644","url":null,"abstract":"Background Coal worker’s pneumoconiosis (CWP) is a chronic occupational disease mainly caused by coal dust inhalation in miners. This study aimed to investigate the clinical value of Osteopontin (OPN), KL-6, Syndecan-4 and Gremlin-1 as serum biomarkers in CWP. Patients and Methods We integrated reported lung tissues transcriptome data in pneumoconiosis patients with silica-exposed alveolar macrophage microarray data to identify four CWP-associated serum biomarkers. The serum concentrations of Osteopontin, Krebs von den Lungen-6 (KL-6), Syndecan-4 and Gremlin-1 were measured in 100 healthy controls (HCs), 100 dust-exposed workers (DEWs) and 200 patients of CWP. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity, specificity, cut-off value and area under the curve (AUC) value of biomarkers. Results The pulmonary function parameters decreased sequentially, and the serum OPN, KL-6, Syndecan-4 and Gremlin-1 concentrations were increased sequentially among the HC, DEW and CWP groups. Among all participants, multivariable analysis revealed that these four biomarkers were negatively correlated with the pulmonary function parameters (all p<0.05). Compared with HCs, patients with higher OPN, KL-6, Syndecan-4 and Gremlin-1 had higher risk for CWP. The combination of OPN, KL-6, and Syndecan-4 can improve the diagnostic sensitivity and specificity of CWP patients differentiated from HCs or DEWs. Conclusion OPN, KL-6 and Syndecan-4 are novel biomarkers that can be used for CWP auxiliary diagnosis. The combination of three biomarkers can improve the diagnostic values of CWP.","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"537-549"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/5c/pgpm-16-537.PMC10241210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9645600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of Methylation Level in the <i>CYP39A1</i> Gene with High Altitude Pulmonary Edema in the Chinese Population.","authors":"Pingyi Wang,&nbsp;Hongyan Lu,&nbsp;Hao Rong,&nbsp;Yuhe Wang,&nbsp;Li Wang,&nbsp;Xue He,&nbsp;Dongya Yuan,&nbsp;Yongjun He,&nbsp;Tianbo Jin","doi":"10.2147/PGPM.S397862","DOIUrl":"https://doi.org/10.2147/PGPM.S397862","url":null,"abstract":"<p><strong>Background: </strong>High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the association between <i>CYP39A1</i> methylation and HAPE.</p><p><strong>Methods: </strong>Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of <i>CYP39A1</i> methylation with HAPE. DNA methylation site in the promoter region of <i>CYP39A1</i> was detected by Sequenom MassARRAY EpiTYPER platform.</p><p><strong>Results: </strong>Probability analysis showed that the methylation probabilities of CYP39A1_1_CpG_5 and CYP39A1_3_CpG_21 are significant differences between the cases and controls (<i>p</i>< 0.05). The methylation level analysis indicated that CYP39A1_1_CpG_2.3.4, CYP39A1_5_CpG_6.7, and CYP39A1_5_CpG_9.10 were higher methylation in HAPE compared to the controls (<i>p</i>< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (<i>p</i>< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, <i>p</i>= 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, <i>p</i>= 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, <i>p</i>= 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, <i>p</i>= 0.033), and CYP39A1_5_CpG_20 (OR 3.05, <i>p</i>= 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, <i>p</i>= 0.016) and CYP39A1_3_CpG_21 (OR 0.18, <i>p</i>= 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, <i>p</i>= 0.014) and CYP39A1_3_CpG_21 (OR 0.08, <i>p</i>= 0.023) had a protective impact on HAPE in people aged ≤32 years. CYP39A1_5_CpG_6.7 (OR 6.70, <i>p</i>= 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, <i>p</i>= 0.008) were related to an increased susceptibility to HAPE aged >32 years. Moreover, the diagnostic value of CYP39A1_3_CpG_21 (AUC = 0.712, <i>p</i>< 0.001) was significantly better than other CpG sites.</p><p><strong>Conclusion: </strong>The methylation level of <i>CYP39A1</i> was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"617-628"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/33/pgpm-16-617.PMC10290841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10095445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps.","authors":"Eda Eken,&nbsp;David S Estores,&nbsp;Emily J Cicali,&nbsp;Kristin K Wiisanen,&nbsp;Julie A Johnson","doi":"10.2147/PGPM.S371994","DOIUrl":"https://doi.org/10.2147/PGPM.S371994","url":null,"abstract":"<p><p>Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of <i>CYP2C19</i> genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of <i>CYP2C19</i> prior to prescribing PPIs. There are strong data to support the influence of <i>CYP2C19</i> genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on <i>H. pylori</i> and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"645-664"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/10/pgpm-16-645.PMC10296543.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang.","authors":"Jia Huang,&nbsp;Haiyan Wu,&nbsp;Guiqiang Zhao,&nbsp;Yan Ma,&nbsp;Yunping An,&nbsp;Li Sun,&nbsp;Fuye Li,&nbsp;Shengling Wang","doi":"10.2147/PGPM.S418722","DOIUrl":"https://doi.org/10.2147/PGPM.S418722","url":null,"abstract":"<p><strong>Background: </strong>Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the development of thyroid dysfunction.</p><p><strong>Methods: </strong>We recruited 183 participants with cretinism and 119 healthy participants from the Xinjiang Uyghur Autonomous Region and randomly selected 29 tag single nucleotide polymorphisms (tSNPs) in <i>TSHB, PAX8, TPO, NKX2-5</i>, and <i>TSHR</i> in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis.</p><p><strong>Results: </strong>Using the chi-squared test, a single SNP was found to be associated with cretinism (recessive model: rs3754363, OR = 0.46, 95% CI = 0.27-0.80, P = 0.00519; genotype model: P = 0.01677). We stratified neurological, myxedematous, and mixed type and determined that another SNP was associated with a higher risk when comparing myxedematous type to the neurological type (rs2277923).</p><p><strong>Conclusion: </strong>rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"785-794"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/b0/pgpm-16-785.PMC10460608.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Influence of Fracture Nonunion (FNU): A Systematic Review.","authors":"Mir Sadat-Ali,&nbsp;Hussain K Al-Omar,&nbsp;Khalid W AlTabash,&nbsp;Ammar K AlOmran,&nbsp;Dakheel A AlDakheel,&nbsp;Hasan N AlSayed","doi":"10.2147/PGPM.S407308","DOIUrl":"https://doi.org/10.2147/PGPM.S407308","url":null,"abstract":"<p><strong>Purpose: </strong>Nonunion of fractures occurs in about 15% of all fractures causing repeated surgical interference and prolonged morbidity. We performed this systematic review to assess genes and polymorphisms influencing fractures' nonunion (FNU).</p><p><strong>Methods: </strong>We searched between 2000 and July 2022 in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Genome Wide Association Studies (GWAS) Catalog, and the Science Citation Index, with the keywords nonunion of fractures, genetic influence, and GWAS. The exclusion criteria were review articles and correspondence. The data were retrieved to determine the number of studies, genes, and polymorphisms and the total number of subjects screened.</p><p><strong>Results: </strong>A total of 79 studies were reported on nonunion of fractures and genetic influence. After the inclusion and exclusion criteria, ten studies with 4402 patients' data were analyzed. Nine studies were case-controlled, and 1 GWAS. It was identified that patients with polymorphisms in the genes <i>ANXA3, BMP2, CALY, CYR61, FGFR1, IL1β, NOG, NOS2, PDGF gene, and TACR1</i> are prone to develop a nonunion of fractures.</p><p><strong>Conclusion: </strong>We believe that for patients who develop an early nonunion of fractures, a genetic study should be conducted for single nucleotide polymorphism (SNP) and genes so that alternative and more aggressive treatment can be performed to heal fractures without prolonged morbidity.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"569-575"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/03/pgpm-16-569.PMC10254683.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library.","authors":"Bi-Hua Luo,&nbsp;Jian-Qing Huang,&nbsp;Chun-Yu Huang,&nbsp;Pan Tian,&nbsp;Ai-Zhen Chen,&nbsp;Wei-Hao Wu,&nbsp;Xiao-Mei Ma,&nbsp;Yue-Xing Yuan,&nbsp;Lian Yu","doi":"10.2147/PGPM.S386085","DOIUrl":"https://doi.org/10.2147/PGPM.S386085","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to screen lymphoma radiotherapy-resistant genes using CRISPR activation (CRISPRa).</p><p><strong>Methods: </strong>The Human CRISPRa library virus was packaged and then transfected into lymphoma cells to construct an activation library cell line, which was irradiated at the minimum lethal radiation dose to screen radiotherapy-resistant cells. Radiotherapy-resistant cell single-guide RNA (sgRNA) was first amplified by quantitative polymerase chain reaction (qPCR) in the coding region and then subject to next-generation sequencing (NGS) and bioinformatics analysis to screen radiotherapy-resistant genes. Certain radiotherapy-resistant genes were then selected to construct activated cell lines transfected with a single gene so as to further verify the relationship between gene expression and radiotherapy resistance.</p><p><strong>Results: </strong>A total of 16 radiotherapy-resistant genes, namely, <i>C20orf203, MTFR1, TAF1L, MYADM, NIPSNAP1, ZUP1, RASL11A, PSMB2, PSMA6, OR8H3, TMSB4Y, CD300LF, EEF1A1, ATP6AP1L, TRAF3IP2</i>, and <i>SNRNP35</i>, were screened based on the NGS results and bioinformatics analysis of the radiotherapy-resistant cells. Activated cell lines transfected with a single gene were constructed using 10 radiotherapy-resistant genes. The qPCR findings showed that, when compared with the control group, the experimental group had significantly up-regulated mRNA expression of <i>MTFR1, NIPSNAP1, ZUP1, PSMB2, PSMA6, EEF1A1</i>, <i>TMSB4Y</i> and <i>TAF1L</i> (p < 0.05). No significant difference in the mRNA expression of <i>AKT3</i> or <i>TRAF3IP2</i> (p > 0.05) was found between the two groups (p > 0.05).</p><p><strong>Conclusion: </strong>The 16 genes screened are potential lymphoma radiotherapy-resistant genes. It was initially determined that the high expression of 8 genes was associated with lymphoma radiotherapy resistance, and these genes could serve as the potential biomarkers for predicting lymphoma radiotherapy resistance or as new targets for therapy.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"67-80"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/ef/pgpm-16-67.PMC9897072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9231261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}