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Different oncological features of colorectal cancer codon-specific KRAS mutations:Not codon 13 but codon 12 have prognostic value

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World Journal of Gastroenterology 2023年第32期29卷 4883-4899页

作者： Hong-Min Ahn Duck-Woo Kim Tae Gyun Lee Hye-Rim Shin In Jun Yang Jeehye Lee Jung Wook Suh Heung-Kwon Oh Sung-Bum Kang Department of Surgery Seoul National University Bundang HospitalSeongnam 13620South Korea Department of Pathology Seoul National University Bundang HospitalSeongnam 13620South Korea Department of Pathology Seoul National University HospitalSeoul 03080South Korea

BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-

关键词： Genes Ras codon Colonic neoplasms Rectal neoplasms

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Deciphering codon usage patterns and evolutionary forces in chloroplast genes of Camellia sinensis var. assamica and Camellia sinensis var. sinensis in comparison to Camellia pubicosta

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Journal of Integrative Agriculture 2019年第12期18卷 2771-2785页

作者： Sophiarani Yengkhom Arif Uddin Supriyo Chakraborty Department of Biotechnology Assam UniversitySilchar 788011AssamIndia Department of Zoology Moinul Hoque Choudhury Memorial Science CollegeAlgapurHailakandi 788150AssamIndia

codon usage bias(CUB) is a unique property of genome which refers to non-random usage of synonymous codons in coding sequences. The present study makes an attempt to find out the pattern of CUB in chloroplast(cp) genes among three tea species, i.e., Camellia sinensis var. assamica(Assam tea), Camellia sinensis var. sinensis(Chinese tea) and Camellia pubicosta(wild tea species) as no work on CUB was reported earlier. To understand the patterns of codon usage among the cp genes of three tea groups, we used bioinformatic tools to investigate the protein coding sequences of cp genes. In our present study, the mean nucleobase T was the highest whereas C was the lowest in all the three tea groups. The overall AT content was more than GC content, i.e., genes were AT rich. The scaled chi-square(SCS) value indicated that the CUB of cp genes was low. The codon CGT(Arg) was over-represented in C. sinensis var. sinensis whereas GGA(Pro) was over-represented in C. pubicosta species. Heatmap study revealed that most of the GC ending codons showed positive correlations between codon usage and GC3 while AT ending codons exhibited negative correlations. From neutrality plot analysis, it was evident that natural selection had played a major role, while mutation pressure exerted a minor effect in the CUB of cp genes in three tea groups. Highly significant(Pcodon usage order(SCUO) of cp genes which suggested that high expression of cp genes was associated with high degree of CUB.

关键词： Camellia sinensis var.assamica Camellia sinensis var.sinensis Camellia pubicosta chloroplast genes codon usage bias mutation natural selection

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p53基因codon72多态性与乳腺癌的相关性研究

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中国肿瘤临床 2010年第9期37卷 499-503页

作者：周晓颖张丽娜赵妍蕊郑红陈可欣乳腺癌防治教育部重点实验室天津市肿瘤防治重点实验室天津医科大学附属肿瘤医院肿瘤流行病与生物统计学研究室天津市300060

目的：研究p53基因codon72多态性与乳腺癌患者的年龄、病理分期、淋巴结转移、雌激素受体（ER）、孕激素受体（PR）、c—erbB-2、P53蛋白表达情况的相关性。方法：TaqMan探针方法检测277例乳腺癌患者血液标本的p53基因codon72多态性。... 详细信息

目的：研究p53基因codon72多态性与乳腺癌患者的年龄、病理分期、淋巴结转移、雌激素受体（ER）、孕激素受体（PR）、c—erbB-2、P53蛋白表达情况的相关性。方法：TaqMan探针方法检测277例乳腺癌患者血液标本的p53基因codon72多态性。免疫组化SP法检测匹配肿瘤纽织中ER、PR、c-erbB-2和P53蛋白的表达情况。SPSS16．0软件行统计学分析，p53基因多态性与病理学特征关系用x^2检验，非条件Logistic回归分析基因多态性与ER、PR、c—erbB-2、P53蛋白表达的相关性，计算OR值及其95％可信区间（95％CI）。P〈0．05为差异有统计学意义。结果：p53基因codon72基因型为CC／CG／GG．频率分别为22．0％、513％和26．7％，携带CC、CG、GG基因型的患者发病年龄逐渐降低，但无统计学差异；p53基因codon72多态性与临床病理学特征无关，与ER、PR、c—erbB-2和P53蛋白表达无相关性（P〉0．05）。肿瘤组织P53蛋白表达与ER、PR、c—erbB-2蛋白表达密切相关（x^2=15．492，P=0．000；x^2=3．970，P=0．046；x^2=17．956，P=0．000）。结论：p53基因codon72多态性与P55蛋白表达及病理学特征无相关性，P53蛋白表达与ER、PR、C—erbB-2蛋白表达关系密切。p53基因codon72基因型与患者发病年龄的关系有待扩大样本量进一步研究。

关键词： p53 codon 72 乳腺癌免疫组化

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ERcodon325、PR＋331G／A与乳腺癌关系的病例对照研究

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肿瘤 2008年第10期28卷 859-863页

作者：靳雅丽沈月平陈锦玲朱岩姚昉张子祥贺天锋苏州大学放射医学与公共卫生学院流行病学与卫生统计教研室江苏省常州市第一人民医院乳腺科常州213003 江苏省常州市钟楼区妇幼保健所常州213000 江苏省常州市卫生局常州213000 苏州大学附属第一人民医院普外科苏州215000

目的：研究雌激素受体（estrogen receptor，ER）codon325、孕激素受体（progestin receptor，PR）＋331G／A基因与乳腺癌的关系以及它们与环境危险因素对乳腺癌的联合作用。方法：采用病例一对照研究的方法，收集206例乳腺癌新发病例... 详细信息

目的：研究雌激素受体（estrogen receptor，ER）codon325、孕激素受体（progestin receptor，PR）＋331G／A基因与乳腺癌的关系以及它们与环境危险因素对乳腺癌的联合作用。方法：采用病例一对照研究的方法，收集206例乳腺癌新发病例，按年龄频数（±3岁）匹配214例健康对照女性。采用结构式调查表收集研究对象的流行病学资料，并采集3mL静脉血。应用荧光定量PCR法检测ERcodon325、PR＋331G／A的基因型。结果：与CC相比，ERcodon325位点CG和GG基因型的调整OR分别为0．99（95％CI：0．61～1．61）和1．13（95％CI：0．62～2．04）；与础相比，PR＋331G／A位点GG基因型的调整OR为1．51（95％CI：O．74—3．07），未发现有增加乳腺癌危险的联合作用（趋势检验：P=0．4090）；与无自然流产史且ERcodon325位点携带CC基因型的妇女相比，有自然流产史且携带CG和GG基因型的妇女OR为3．57（95％CI：1．21—10．52），相加模型检验接近有统计学意义（S=3．06，AP=0．97，u=1．8981，P=0．0588）。结论：ERcodon325、PR＋331G／A单基因多态性可能与乳腺癌发病风险无关，ERcodon325多态性与自然流产史具有增加乳腺癌危险的联合作用趋势。

关键词：乳腺肿瘤多态性单核苷酸 ER codon 325 PR+331G/A 联合作用

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Analysis of codon Usage Pattern of Banana Basic Secretory Protease Gene

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Plant Diseases and Pests 2019年第1期10卷 1-4,9页

作者： Mensah Raphael Anue Sun Xueli Cheng Chunzhen Lai Zhongxiong College of Horticulture/Institute of Horticultural Biotechnology Fujian Agriculture and Forestry University

[Objective] The objective of this study was to understand the codon usage bias pattern of banana pathogenesis-related 17 gene, Basic Secretory Protease gene(MaBSP). [Method] Relative codon usage patterns of MaBSP were calculated using the software codonW version 1.4.2. and the web-based tool(http://kazusa.***.jp/codon/).[Result] Our findings showed that C-ended and G-ended codons were the most preferential except the TER codon UGA which was coded for by just one codon. The ENc value, relationship between AT bias and GC bias, Random synonymous codon usage(RSCU) and CAI all showed that codon bias usage existed in MaBSP gene.[Conclusion] The codon usage patterns of MaBSP gene is principally influenced by natural selection in the third position. However, other multiple factors also influence this pattern.

关键词： codon usage codon bias Natural selection Mutation bias Random synonymous codon usage Pathogenesis-related(PR)gene

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Successful expression and purification of dppd, using a codon optimized synthetic gene

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Open Journal of Immunology 2011年第1期1卷 1-7页

作者： Suely S. Kashino Antonio Campos-Neto The Forsyth Institute Global Infectious Disease Research Center Boston USA.

DPPD (Rv0061) is a difficult to express protein of Mycobacterium tuberculosis that elicits strong and specific delayed type hypersensitiv-ity reactions in humans infected with M. tuber-culosis. Therefore DPPD is a molecule that can improve the specificity of the tuberculin skin test, which is widely used as an aid for the di-agnosis of tuberculosis. However, a pitfall of our initial studies was that the DPPD molecule used to perform the skin tests was engineered as fu-sion molecule with another Mycobacterium protein. This approach was used because no expression of DPPD could be achieved either as a single molecule or as a fusion protein using a variety of commercially available expression systems. Here, we report the production and purification of rDPPD using a synthetic gene engineered to contain E. coli codon bias. The gene was cloned into pET14b expression vector, which was subsequently used to transform Rosetta 2(DE3)pLysS or BL-21(DE3)pLysS host cells. The recombinant protein was over-ex- pressed after induction with IPTG and its puri-fication was easily achieved at levels of 5 – 10 mg/l of bacterial broth cultures. The purified protein was confirmed to be DPPD by Mass Spectroscopy sequencing analysis. Moreover, purified rDPPD stimulated peripheral blood mononuclear cells of PPD positive blood do-nors to produce high levels of IFN-γ, thus con-firming that this molecule is biologically active. Because of the DPPD gene is restricted to the tuberculosis-complex organisms of Mycobacte-rium genus, this highly purified molecule should be useful for the identification of indi-viduals sensitized with tubercle

关键词： Mycobacterium tuberculosis DPPD codon Bias

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α2珠蛋白基因codon 31(AGG>AAG)突变导致α地中海贫血的研究

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广西医科大学学报 2018年第6期35卷 809-812页

作者：黄紫娟张学陈萍陈文强李树全丘玉铃肖璇杨德寨广西医科大学第一附属医院地方病科中国医学科学院地中海贫血防治研究重点实验室南宁530021

目的:分析广西地区血红蛋白H病(Hb H病)的基因突变类型,并对先证者进行家系调查。方法:对2016年10月至2017年11月在广西医科大学第一附属医院经血常规、血红蛋白(Hb)分析确诊为Hb H病的360例患者,利用荧光PCR熔解曲线分析法及DNA测序方... 详细信息

目的:分析广西地区血红蛋白H病(Hb H病)的基因突变类型,并对先证者进行家系调查。方法:对2016年10月至2017年11月在广西医科大学第一附属医院经血常规、血红蛋白(Hb)分析确诊为Hb H病的360例患者,利用荧光PCR熔解曲线分析法及DNA测序方法进行α地中海贫血基因突变分析。结果:在360例Hb H病患者中发现1例罕见的非缺失型Hb H病。病例为女性,广西北海人,1岁,无黄疸、肝脾肿大等,未输过血。血常规结果显示:RBC 3.75×1012/L,Hb 77.3g/L,MCV 69.05fL,MCH 20.62pg,MCHC 296.9g/L,HCT 0.26。Hb分析Hb H+Hb Bart’s 20.1%,基因分析结果显示,α2珠蛋白基因codon 31(AGG>AAG)突变复合东南亚缺失型α地中海贫血-1(--SEA/αCD31α)。患者的家系分析显示,其父亲的血常规及血红蛋白分析正常,基因分析为α2蛋白基因codon 31突变杂合子。母亲为东南亚缺失型α地中海贫血-1杂合子。结论:首次在广西地区检出α2珠蛋白基因codon 31AGG>AAG基因突变。codon 31AGG>AAG基因突变导致α地中海贫血,当复合东南亚缺失型α地中海贫血-1时有中度贫血。首次发现其杂合子无临床症状,血液学检测正常,临床上较容易误诊和漏诊。

关键词： α地中海贫血 Hb H病 codon 31(AGG〉AAG)突变基因型

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codon bias of influenza a viruses and their hosts

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American Journal of Molecular Biology 2011年第3期1卷 174-182页

作者： Keli C. Fancher Wei Hu Department of Computer Science Houghton College

The Influenza A virus remains an annual and worldwide health concern due to its fast evolutionary rate. There are two major forms of Influenza evolution: drift, caused by mutations, and shift, which results from the exchange of genetic information between two gene segments. Using six synonymous codon usage bias indexes (GC content, ENC, SCUO, codon Volatility, RSCU, and Odds Ratio), this study revealed the evolutionary drift patterns in the Influenza A viruses of avian, human, and swine origins as well as those of their hosts. We found that the variation of GC content across the 11 genes in Influenza A uniquely determines the viral origins in avian, human, and swine hosts. As was previously noticed in the Flaviviridae virus, a codon’s RSCU value of the Influenza viruses is positively correlated to the Odds Ratio of the dinucleotides contained within that codon. Additionally, the RSCU values of avian, human, and swine viruses and their corresponding hosts are similar, which is also true of Odds Ratio. Furthermore, the GC content, ENC, SCUO, and codon Volatility are similar across the avian, human, and swine hosts;however, the RSCU and Odds Ratio of the hosts are distinct. Our findings expanded the knowledge on codon bias of Influenza viruses and their hosts.

关键词： Influenza A Evolutionary Drift codon Bias

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codon 249 mutations of p53 gene in development of hepatocellular carcinoma

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World Journal of Gastroenterology 1998年第2期4卷 33-35页

作者： Peng, XM Peng, WW Yao, JL Sun Yat Sen Univ Med Sci Affiliated Hosp 3 Dept Infect Dis Guangzhou 510630 Guangdong Provi Peoples R China

Ｃｏｄｏｎ２４９ｍｕｔａｔｉｏｎｓｏｆｐ５３ｇｅｎｅｉｎｄｅｖｅｌｏｐｍｅｎｔｏｆｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａＰＥＮＧＸｉａｏＭｏｕ，ＰＥＮＧＷｅｎＷｅｉａｎｄＹＡＯＪｉＬｕＳｕｂｊｅｃｔｈｅ... 详细信息

Ｃｏｄｏｎ２４９ｍｕｔａｔｉｏｎｓｏｆｐ５３ｇｅｎｅｉｎｄｅｖｅｌｏｐｍｅｎｔｏｆｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａＰＥＮＧＸｉａｏＭｏｕ，ＰＥＮＧＷｅｎＷｅｉａｎｄＹＡＯＪｉＬｕＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｎｅｏｐｌａ...

关键词： liver neoplasms carcinoma, hepatocellular p53 gene mutation RNA, messenger LOH codon 249 immunohisto chemistry polymerase chain reaction

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Use of a naturally occurring codon bias for identifying topoisomerase mutations in ciprofloxacin resistant <i>Escherichia coli</i>using PCR and future prospects with other bacterial genera: A pilot study

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Advances in Biological Chemistry 2012年第4期2卷 366-371页

作者： Subramanian Krishnan Dheepikaa Balasubramanian B. Appala Raju Baddireddi Subadhra Lakshmi Department of Microbiology PSG Institute of Medical Sciences and Research Coimbatore India Division of Infectious Diseases Department of Pediatrics The Saban Research Institute Children’s Hospital Los Angeles University of Southern California School of Medicine Los Angeles USA Tissue Culture and Drug Discovery Laboratory Centre for Biotechnology Anna University Chennai India

We developed a novel PCR method aimed at identi- fying and amplifying native codon sequences of muta- tion-prone amino acids in DNA gyrase implicated in quinolone resistance using a naturally occurring co- don bias in... 详细信息

关键词： Escherichia coli Gyrase A codon Bias Mutation Ciprofloxacin Resistance PCR

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