Values of mutations of K-ras oncogene at codon 12 in detection of pancreatic cancer:15-year experience

AIM:To summarize progress in the study of K-ras gene studies in pancreatic cancer and its potential clinical significance in screening test for early detection of pancreatic cancer,and to differentiate pancreatic cancer from chronic pancreatitis in recent decade.METHODS:Literature search (MEDLINE 1986-2003) was performed using the key words K-ras gene, pancreatic cancer, chronic pancreatitis, and diagnosis. Two kind of opposite points of view on the significance of K-ras gene in detection early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis were investigated.The presence of a K-ras gene mutation at codon 12 has been seen in 75-100% of pancreatic cancers, and is not rare in patients with chronic pancreatitis, and represents an increased risk of developing pancreatic cancer. However,the significance of the detection of this mutation in specimens obtained by needle aspiration from pure pancreatic juice and from stools for its utilization for the detection of early pancreatic cancer, and differentiation pancreatic cancer from chronic pancreatitis remains controversial.CONCLUSION:The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertains in clinical pratice. Nevertheless, K-ras mutation screening may increase the sensitivity of FNA and ERP cytology and may be useful in identifying pancreatitis patients at high risk for developing cancer, and as a adjunct with cytology to differentiate pancreatic cancer from chronic pancreatitis.

Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

AIM:To investigate frequency and clinical significance of K-ras mutations in pancreatic diseases and to identify its diagnostic values in pancreatic carcinoma.METHODS:117 ductal lesions were identified in the available sections from pancreatic resection specimens of pancreatic ductal adenocarcinoma, comprising 24 pancreatic ductal adenocarcinoma, 19 peritumoral ductal atypical hyperplasia, 58 peritumoral ductal hyperplasia and 19 normal duct at the tumor free resection margin. 24 ductal lesions were got from 24 chronic pancreatitis. DNA was extracted.Codon 12 K-ras mutations were examined using the two-step polymerase chain reaction (PCR) combined with restriction enzyme digestion,followed by nonradioisotopic single-strand conformation polymorphism (SSCP) analysis and by means of automated DNA sequencing.RESULTS: K-ras mutation rate of the pancreatic carcinoma was 79%(19/24) which was significantly higher than that in the chronic pancreatitis 33%(8/24) (P<0.01). It was also found that K-ras mutation rate was progressively increased from normal duct at the tumor flee resectbn margin, peritumoral ductal hyperplasia, peritumoral ductal atypical hyperplasia to pancreatic ductal adenocardnoma. The mutation pattern of K-ras 12 codon of chronic pancreatitis was GGT→GAT, GGT and CGT,which is identical to that in pancreatic carcinoma.CONCLUSION:K-ras mutation may play a role in the malignant transformation of pancreatic ductal cell. K-ras mutation was not specific enough to diagnose pancreatic carcinoma.

Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

K-ras基因突变与胃癌组织病理特征及预后的相关性分析

目的 探讨与分析K-ras基因突变与胃癌组织病理特征及预后的相关性。方法 选取100例胃癌患者作为胃癌组,选择同期在本院体检的健康人群100例作为对照组,检测所有对象的外周血K-ras基因突变情况。调查胃癌患者的组织病理特征,随访患者的预后并进行相关性分析。结果 胃癌组的K-ras基因突变率显著高于对照组,差异有统计学意义(P<0.05)。在胃癌组中,不同胃癌组织病理特征(病灶直径、组织学分化、临床分期、淋巴结转移)患者的K-ras基因突变率对比差异均有统计学意义(P<0.05)。胃癌患者平均随访时间(35.59±1.19)月,其中死亡18例,死亡患者的K-ras基因突变率显著高于生存患者,差异有统计学意义(P<0.05)。在胃癌组中,Spearman分析显示K-ras基因突变率与病灶直径、组织学分化、临床分期、淋巴结转移、预后死亡等存在正相关性(P<0.05)。结论 胃癌患者多伴随有血清K-ras基因突变,与患者的临床病理特征与预后死亡存在相关性,K-ras基因突变具有重要的临床应用价值。

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

Promoter hypermethylation of tissue specific tumor supressor genes and point mutation in K-ras, c-myc proto-oncogenes in urinary (transitional cell) bladder carcinoma

In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high grade and proliferation index. Mutated K-ras proto-onco- gene profiles were detected in 17 (21%) tumoral spiecemens that examined. Tumor specimens were also showed hypermethylated promoter domain for the SFRP2, MGMT tumor supressor genes. These findings showed the combine effect of mutated c-myc and K-ras oncogene and epigenetic inactivation of tissue specific tumor supressor genes (TS) play a crucial role in tumor progression and recurrence in UN carcinogenesis.

K-Ras、BRAF、PIK3CA基因突变与直肠癌新辅助放化疗疗效及预后的关系

目的:探讨K-Ras、BRAF、PIK3CA基因突变与直肠癌新辅助放化疗(nCRT)疗效及预后的关系。方法:选取2015年03月至2020年03月于医院接受nCRT并行根治手术的直肠癌患者182例作为研究对象。所有患者术前接受卡培他滨化疗,同时采用长程分割疗法进行放疗,共治疗5周,nCRT结束后5~12周,根据肿瘤位置及nCRT情况行手术治疗,出院后进行为期1年的随访。以肿瘤退缩分级(TRG)评价直肠癌nCRT疗效,TRG 1-3级纳入nCRT有效组,TRG 4-5级纳入nCRT无效组。nCRT前经肠镜取肿瘤组织,检测K-Ras、BRAF、PIK3CA基因突变状态,分析K-Ras、BRAF、PIK3CA基因突变与直肠癌nCRT疗效及预后的关系。结果:在182例直肠癌患者中,K-Ras、BRAF、PIK3CA基因突变率分别为34.07%、6.59%、13.19%,nCRT治疗有效率为60.44%。nCRT有效组K-Ras、BRAF及PIK3CA基因突变率显著低于nCRT无效组(P<0.05)。K-Ras、BRAF、PIK3CA基因突变状态预测直肠癌nCRT疗效的敏感度分别为68.45%、65.38%、57.76%,特异度分别为72.39%、69.23%、63.12%,AUC分别为0.626、0.573、0.532。Logistic回归分析结果显示K-Ras、BRAF、PIK3CA基因突变与直肠癌nCRT疗效显著相关(P<0.05)。K-Ras、BRAF、PIK3CA基因突变患者平均生存时间均分别短于K-Ras、BRAF、PIK3CA无突变者,差异有统计学意义(P<0.05)。多变量COX回归分析结果显示K-Ras、BRAF及PIK3CA基因突变患者死亡风险分别是K-Ras、BRAF、PIK3CA无突变者的1.639倍、1.811倍、1.432倍(P<0.05)。结论:K-Ras、BRAF、PIK3CA基因突变与直肠癌患者nCRT疗效和预后相关,可作为nCRT疗效和预后的预测指标。

1889例结直肠癌MSI、K-ras、N-ras和B-raf基因状态以及临床病理特征分析

目的通过对1889例结直肠癌微卫星不稳定(MSI)、K-ras、N-ras和B-raf基因检测,分析其基因状态与临床病理特征之间的关联性。方法收集东部战区总医院病理科结直肠癌患者手术切除大标本共计1889例,通过PCR荧光法联合毛细管电泳法对1889例结直肠癌进行MSI、K-ras、N-ras和B-raf检测,分析其基因状态与临床病理特征之间的关系,以及MSI与K-ras、N-ras和B-raf之间的关联性分析,并且对MSI自身位点的相关性分析。结果1889例结直肠癌患者中,微卫星高度不稳定(MSI-H)更易发生于右侧结肠(16.4%)、黏液腺癌(14.9%)、分化程度较低(18.7%)、年龄偏低(8.3%)、淋巴结未转移(9.1%)以及B-raf突变(5.2%)的患者中,K-ras突变更易发生于右侧结肠(50.7%)、黏液腺癌(50.7%)、分化程度较高(52.1%)、微卫星低度不稳定或稳定型(42.2%)的患者中,而B-raf突变更易发生在MSI-H(6.9%)的患者中,而N-ras基因则与临床病特征关联性不强。结论结直肠癌患者的MSI、K-ras和B-raf基因状态与临床病理特征存在着高度的关联性,因此通过分析其基因状态与临床病理特征之间的关系可以为临床靶向治疗以及预后提供更加可靠的依据。

曲美替尼对K-ras突变直肠癌细胞恶性行为、耐药蛋白及巨噬细胞极化的作用机制的研究

目的探讨曲美替尼对K-ras突变直肠癌细胞恶性行为、耐药蛋白及巨噬细胞极化的作用机制。方法取K-ras突变直肠癌细胞HCT116,将其随机分为HCT116组(HC组)、西妥昔单抗+HCT116组(CE组)、低剂量曲美替尼+HCT116组(LT组)、中剂量曲美替尼+HCT116组(MT组)、高剂量曲美替尼+HCT116组(HT组),Transwell实验及划痕实验检测细胞恶性行为,MTT法检测药物敏感性,RT-PCR法检测耐药蛋白表达,免疫印迹法检测巨噬细胞极化相关指标。结果与HC组相比,其余四组细胞侵袭、迁移及GST-π、P-gp、TopoⅡ、CD163表达显著降低(P<0.05),CD40蛋白表达显著升高(P<0.05);与LT组相比,MT组、HT组细胞侵袭、迁移及GST-π、P-gp、TopoⅡ、CD163表达显著降低(P<0.05),CD40蛋白表达显著升高(P<0.05),且HT组比MT组变化明显(P<0.05);HCT116细胞对西妥昔单抗与曲美替尼均敏感,但与西妥昔单抗相比,曲美替尼的IC_(50)明显更低(P<0.05)。结论曲美替尼对K-ras突变直肠癌细胞具有显著疗效,可显著改善其恶性行为,抑制耐药蛋白表达,抑制巨噬细胞M2极化。

人恶性胸膜间皮瘤组织中K-ras基因点突变的研究

目的:探究云南省大姚县青石棉污染区恶性胸膜间皮瘤(MPM)患者组织K-ras基因点突变。方法:应用聚合酶链式反应(PCR)-单链构象多态性分析和PCR-DNA测序技术联合检测59例MPM患者和13例非MPM患者胸膜间皮组织中K-ras基因密码子12、13和61的点突变情况。结果:59例MPM患者和13例非MPM患者胸膜间皮组织中均没有发生K-ras基因点突变,K-ras基因点突变的检出率为0.0%。结论:云南省大姚县青石棉污染区MPM患者组织K-ras基因突变型的比例较低,提示K-ras原癌基因点突变在此地区MPM的诱导发生中并不发挥关键作用。

TCGA-based analysis of oncogenic signaling pathways underlying oral squamous cell carcinoma

Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.

结直肠癌APC、K-ras、p53基因突变检测

目的:探讨结直肠癌中APC、K-ras、p53基因突变模式。方法:应用酚/氯仿法提取48例结直肠癌组织及其相应正常黏膜组织的DNA,用聚合酶链反应(PCR)、单链构象多态性分析(SSCP)和DNA测序等方法检测APC基因第15外显子突变密集区(mutation cluster region,MCR)区段、K-ras和p53基因的突变。结果:APC、K-ras和p53基因的突变率分别为37.5%(18/48)、43.8%(21/48)和35.4%(17/48)。48例结直肠癌组织中,有42例发生APC、K-ras或p53基因突变,突变率高达87.5%(42/48),其中仅有APC、K-ras或p53 1种基因发生突变的发生率分别为16.7%(8/48)、25.0%(12/48)和20.8%(10/48)。单独1种基因发生突变的总发生率为62.5%(30/48)。APC和p53,APC和K-ras或p53和K-ras 2种基因均有突变的发生率分别为6.3%(3/48)、10.4%(5/48)和4.2%(2/48)。APC、K-ras和p53 3种基因均发生突变的发生率为4.2%(2/48)。2种和3种基因均发生突变的总发生率为25%(12/48)。结论:结直肠癌的发生、发展并不完全遵循由正常结直肠黏膜上皮细胞向腺瘤和侵袭性癌转化的过程中,及依次发生“APC→K-ras→p53→DCC”突变累积这一经典的结直肠癌发生发展模式,可能存在其他结直肠癌发病机制。

癌性胸腔积液K-ras基因突变检测及临床应用

目的：探讨Ｋ－ｒａｓ 基因突变检测用于癌性胸腔积液的诊断价值。方法：采用ＰＣＲ－ ＳＳＣＰ技术对５８ 例癌性及３０ 例结核性胸腔积液进行Ｋ－ｒａｓ 基因突变分析。结果：结核性胸液未发现突变，癌性胸液有１７ 例突变阳性，突变率２９－３ ％ ，其中腺癌所致胸腔积液突变率为３４－１％ （１４／２１），鳞癌１６－７ ％（２／１２）。１７ 例Ｋ－ｒａｓ 基因突变阳性的胸液中，１４ 例为肉眼血性，明显高于非血性胸液组，Ｐ＜ ０－０５。１８ 例未找到原发病灶的胸液中４４－４％ Ｋ－ ｒａｓ 基因突变阳性。４９ 例患者随访１０ 个月，Ｋ－ｒａｓ 基因突变阳性者死亡率高达８０－０ ％ ，而无Ｋ－ｒａｓ 基因突变者死亡率明显降低，为２６－５ ％ ，Ｐ＜ ０－０５ 。结论：Ｋ－ｒａｓ 基因突变检测是诊断癌性胸腔积液的又一有效手段，在某些情况下显示出特有的优势，并且对预后的判断有一定价值。

非小细胞肺癌中EGFR和K-ras基因突变与蛋白表达相关性的研究

背景与目的:当前表皮生长因子受体(epidermal growth factor receptor,EGFR)基因靶向治疗已成为晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)治疗的研究的热点之一。本研究旨在探讨NSCLC患者中EGFR基因和K-ras(Kirsten rat sarcoma viral oncogene)基因突变的情况,分析其与蛋白表达的相关性及对吉非替尼(gefitinib)治疗的指导意义。方法:收集200例NSCLC患者新鲜组织,采用基因测序法检测EGFR及K-ras基因突变的状态;同时采用免疫组织化学法检测EGFR和K-ras蛋白的表达。结果:200例患者中,EGFR基因突变率为33%,主要发生在19号和21号外显子;K-ras基因突变率为5.5%,主要位于第12密码子;不存在同时携带有EGFR和K-ras两种基因突变的病例。腺癌尤其是含细支气管肺泡癌(bronchioloalveolar carcinoma,BAC)病理分型的患者、非吸烟患者和女性患者EGFR突变率较高。EGFR蛋白表达阳性率为16%,与总的EGFR突变无关(P>0.05),但与19号外显子突变具有统计学意义(P<0.05)。K-ras蛋白表达阳性率为52.5%,与K-ras基因突变无关(P>0.05)。15例携带有EGFR基因突变的NSCLC患者服用吉非替尼,12例(其中8例为EGFR蛋白表达阴性)有效。结论:EGFR蛋白表达与EGFR基因19号外显子突变具有一定相关性;联合检测EGFR和K-ras基因突变可用来筛选对EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗敏感的人群,并预测吉非替尼治疗晚期NSCLC的疗效及预后。

XELOX和OLF化疗方案治疗K-ras基因突变型老年晚期大肠癌的疗效分析

目的比较分析K-ras基因突变型老年晚期大肠癌患者接受奥沙利铂联合卡培他滨(XELOX)和奥沙利铂联合氟尿嘧啶(OLF)化疗方案的疗效。方法分析2009年1月-2012年8月该院收治的经基因分析确诊为K-ras基因突变型晚期大肠癌病例,共106例。其中接受XELOX化疗者56例,接受OLF化疗者50例,并比较分析两组接受化疗后发生毒副反应、客观缓解率、疾病控制率、无进展生存期、总生存期的差异。结果O LF组骨髓抑制、恶心呕吐、静脉炎、心脏毒性的发生率高于XELO X组,而腹泻的发生率XELO X组要明显高于OLF组,在口腔炎及神经毒性的发生率上,两组差异无统计学意义。两组客观缓解率、疾病控制率、无进展生存期和总生存期差异无统计学意义。结论 XELOX治疗K-ras基因突变型老年晚期结肠癌具一定疗效,相对安全,可提高患者的生存质量。

粪便中检测K-ras基因突变对老年大肠癌诊断价值的研究

探讨粪便K ras基因检测在老年大肠癌临床诊断中的价值。收集连续就诊的 2 3例老年大肠癌患者、2 0例结肠腺瘤性息肉患者及 2 0名健康老年查体者的粪便 ,并从中提取DNA ,应用等位基因特异性杂交技术检测粪便K ras基因第 12位密码子第 1、2位碱基突变情况。结果K ras基因突变率在大肠癌患者为 5 6 5 2 % (13/ 2 3) ,明显高于正常查体者的 5 % (1/ 2 0 ) (P <0 0 1) ,与结肠腺瘤性息肉组的 30 % (6 / 2 0 )比较 ,差异无显著性意义 (P >0 0 5 )。 92 31% (12 / 13)的大肠癌K ras基因突变位点发生在第 12位密码子第 2位碱基。研究表明 ,结肠癌患者组织及粪便中K ras基因突变的检出具有良好的一致性 ,提示粪便中检测K

电化学发光-聚合酶链式反应方法检测胰腺癌中K-ras基因点突变

发展了一种可用于快速检测胰腺癌中K-ras癌基因点突变的电化学发光-聚合酶链式反应(ECL-PCR)分析方法。该法采用三联吡啶钌标记的上游引物和生物素标记的下游引物对目的片段进行PCR扩增;再采用限制性内切酶MvaI对扩增产物进行酶切。由于野生型样品和突变型样品间存在酶切位点的变化,其中只有野生型样品能被切断;通过生物素与链霉亲和素包被的磁珠连接,将生物素标记的DNA片段收集到检测池中,进行电化学发光检测。采用该法对13例胰腺癌组织中的K-ras癌基因第12位密码子进行点突变分析,只需要10μL样品、20min孵育时间和30s采集时间,就可得出其中有12例存在点突变,点突变率为92.3%。本方法操作简便、安全、快速、灵敏,可用于检测任何一种导致限制性内切酶位点改变的基因点突变。

非小细胞肺癌中EGFR和K-ras基因突变检测分析与病理特征的关系

目的探讨不同分型非小细胞肺癌的EGFR与K-ras基因突变及其相关病理特征的关系。方法基因测序方法检测260例非小细胞肺肿瘤患者肿瘤组织中的EGFR(18,19,20,21外显子)和K-ras(12,13,61密码子)基因的突变。结果 260例样本中,EGFR基因突变检出率为48.8%(127/260),突变主要集中在19号外显子的缺失和21号外显子的点突变。K-ras基因突变检出率为10%(26/260),其中12、13和61密码子均发现突变。受检的所有样本中没有发现EGFR与K-ras基因同时出现突变的情况。腺癌的EGFR突变检出率明显高于鳞状细胞癌等其他组织类型。在分化程度上,高分化与中分化癌基因突变检出率和中分化与低分化突变检出率比较差异显著(P<0.01)。EGFR突变与有无淋巴结转移无关(P>0.05)。K-ras基因突变与组织类型、患者性别、分化程度、有无淋巴结转移间无相关性。结论非小细胞肺癌EGFR基因突变检出率较高,K-ras基因突变检出率较低,且两种突变并不同时出现。EGFR基因突变与性别、肺癌组织类型、分化程度有关,存在多种突变。

肺癌K-ras基因突变的二步PCR检测及其临床应用

目的 探讨高敏感性Kras基因点突变检测方法在肺癌临床的应用价值。方法 应用二步(巢式)聚合酶链反应结合限制性片断多态性分析方法(PCRRFLP)检测临床肺癌标本Kras基因第12密码子点突变。结果 二步PCRRFLP法检测Kras点突变的敏感性较一步法提高约64倍。55例肺癌石蜡包埋标本中,Kras点突变检出率为47.3%;对另67例纤支镜标本进行基因检测,以Kras突变进行基因诊断的敏感性为70.9%,特异性为91.7%。结论 二步PCRRFLP法对临床肺癌标本Kras点突变检出率较高。