Effects of endotoxin on expression of ras, p53 and bcl-2 oncoprotein in hepatocarcinogenesis induced by thioacetamide in rats

AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]

APC and K-ras gene mutation in aberrant crypt foci of human colon

AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .

Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection

AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.

Detection of k-ras gene point mutation in fine needle aspiration and pancreatic juice by sequence special primer method and its clinical significance

INTRODUCTIONThe point mutation rate of k-ras gene at codon 12 inpancreatic adenocarcinoma is reported to be as highas 90%,and with no mutations in normalpancreas tissues or other pancreatic disorders.Wehave detected the presence of k-ras gene

Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas

IM To study the relationship between Nras gene mutation and p53 gene expression in the carcinogenesis and the development of human hepatocellular carcinomas (HCC).METHODS The Nras gene mutation and the p53 gene expression were analyzed in 29 cases of HCC by polymerase chain reactionsingle strand conformation polymorphism (PCRSSCP) and immunohistochemistry.RESULTS Thirteen cases of HCCs were p53 positive (448%), which showed a rather high percentage of p53 gene mutation in Guangxi. The aberrations at Nras codon 2-37 were found in 7931% of HCCs and 8077% of adjacent nontumorous liver tissues. More than 2 point mutations of Nras gene were observed in 22 cases (7586%). Twelve cases (4137%) of HCCs showed both Nras gene mutation and p53 gene expression.CONCLUSIONS Nras gene and p53 gene may be involved in the carcinogenesis and the development of HCC. That 38% of HCCs with Nras gene mutation did not express p53 protein indicates that some other genes or factors may participate in the carcinogenesis and the development of HCC.

Studies on the relationship between the point mutation of ras oncogenes and the prognosis of patients with gastric cancer

AIM To study the relationship between the point mutation of ras oncogenes and the prognosis of patients with gastric cancer.

Expressions of myc and ras gene in human hepatocellular carcinoma by applying the double hybridization in situ

Objective: To establish a method of non-isotope double in situ hybridization in order to detect the expression of two kinds of oncogenes at single cell level simultaneously, and confirm the hypothesis of 'model of stepwise carcinogenesis'. Methods: The method of non-isotope double in situ hybridization was established with the digoxigenin (Dig) and biotin(Bio) labelled probes. The expression of two members of oncogenes of the myc and/or ras gene families (myc and N-ras, myc and K-ras, myc and H-ras, N-ras and K-ras , N-ras and H-ras, K-ras and H-ras) was further studied with the method in 10 cases of Chinese Hepatocellular Carcinomas (HCC). Results : Co-expression of two kinds of oncogenes was detected only in a few cases, reflected by coshowing two different hybridization signals ,i. e. , co-showing of Dig-myc and Bio-H-ras, Dig-myc and Bio-N-ras, Dig-myc and Bio-K-ras was observed in 2 cases, 2 cases and one case, respectively. The common characteristics were that positive cells of myc distributed diffusely, while positive cells of ras diatributed sporadically or locally among the positive cells of myc, and only a few cells exhibited co-showing of two oncogenes at single cell level. There were only 2 cases representing co-showing of two oncogenes in ras gene family (Dig-N-ras and bio-H-ras, Dig-N-ras and Bio-K-ras , respectively). The two kinds of positive cells of different ras gene represented mixed local and sporadical distribution, and co-showing of two signals was found in a few cells at single cell level. Conclusion: There are multiple oncogenes involving in tumorigenesis by their ordered activation. The activation of the ras gene family plays a role in promotion, while the activation of myc is an important event in late stage of tumorigenesis

The Role of Ras Gene Mutation in Gastric Cancer and Precancerous Lesions

Abnormality of ras gene family was studied in a total of 206 cases of gastric cancer and precancerous lesions by PCR-RFLP, PCR-SSCP and DNA sequencing. The results showed that mutation rate of H-ras 12 codon in metaplasia,atypical hyperplasia, early-stage cancer and advanced cancer was 16. 7%, 31. 2 %, 50. 0%, and 32. 2%, respectively. In the groups of superficial gastritis and normal controls, no mutation were detected in codon 12 of ras. Mutations of Hras 61 codon and N-ras 12 codon in various groups were the same as those in normal control. K-ras 12 codon mutation was detected in only 2 cases of gastric cancer by using PCR-SSCP, but it was not detected by DNA sequencing, which may be polymorphism. All H-ras 12 codon mutations were G→T mutation. There were significant difference between the groups of metaplasia, dysplasia, gastric carcinoma and normal control group (P<0.05, P<0.01, P<0.01,respectively). It was concluded that H-ras 12 codon mutation was an early event and may play an important role in gastric carcinogenesis. Although K-ras, N-ras mutation rates are high in colon cancer and leukemia, it seems to bear no relationship with gastric cancer.

In Vitro Anti-tumor Immune Response Induced by Dendritic Cells Transfected with Recombinant Adenovirus Carrying Mutant K-ras Genes

Summary： The specific anti-tumor immune response induced by mouse bone marrow dendritic cells （DCs） lransfected with recombinant adenovirus carrying mutant k-ras genes was investighted. DCs were generated from mouse bone marrow in the presence of rmGM-CSF （3.3 ng/mL） and rmIL-4 （1.3 ng/mL） and detected by FACS, and then transfecled with the recombinant adenovirus encoding mutant k ras gene. The efficacy of transfection and T cell stimulating activity of DCs were detected. CTL activity of the mice vaccinated with DCs was observed. The resuhs showed thai DCs had dendritic veiled morphology. BmDCs highly expressed B7-1（80%）, B7-2（77%）, MHC Ⅱ （70%）, CDllc （65%）, CD40 （70%） and CD54 （96%） with FACS, and no significant difference in the expression was observed before and after the transfection （P〈0.05）. The DCs transfeeled by mutant k-ras gene could significantly stimulate lymphoeytes proliferation as compared with those transfeeted by Ad e or non-modified DCs （P〈0.05）. DC vaccine transfected by mutant k-ras gene could induce CTL activity against Lewis lung cancer, but not against B16. The specific eytotoxicity against Lewis lung cancer in Ad-k-ras/12-transdueed DC group was signifieantly higher than those in the control, vector and non transfeeted DCs groups （P〈0.05）. It was concluded that special antitumor response could be induced by DCs transfected with recombinant adenovirus carrying mutant k-ras genes.

Rapid Detection ofK-ras Gene Point Mutation at Codon 12 by PCR-SSPin Pancreatic Adenocarcinom a

To evaluate the feasibility and clinical significance of the PCR SSP technique in detecting K ras gene mutation at codon 12 in pancreatic adenocarcinoma tissues. 80 specimens of surgical resection or biopsy samples were tested at our hospital from January 1994 to September 1995. Three different special sequence primers (SSP) synthesized according to mutation styles of CGT, GTT, GAT were respectively prepared. Three amplification reactions were performed for each sample. The amplification products were analyzed by conventional polyacrylamide gel electrophoresis, stained with ethidium bromide and observed under UV transillumination. Results: All of the 34 pancreatic adenocarcinoma samples had positive PCR results with the mutation rate 100%. 7 cases were CGT mutation, 18 GGT and 17 GAT mutation, in which 2 types of mutation existed in 8 cases. No mutation appeared in 13 normal pancreatic tissues, 6 insulinomas, 6 chronic pancreatitis, 5 benign pancreatic cysts, 7 bile duct carcinoma, 5 ampulla carcinoma and 4 carcinomas of duodenal papilla. Conclusion: Pancreatic adenocarcinoma is one of the commonly encounted tumors and is still very difficult to diagnose at the early stage and to distinguish from other lesions preoperatively. Our study indicates that PCR SSP is an ideal assay in comparison with other methods to detect K ras gene mutation. It is simple, rapid, specific, sensitive and easily generalized for clinical application on preoperative diagnosis.

Study of mutations of p53, APC and K-ras genes in 47 cases of intestinalmetaplasia of gastric mucosa

Objective:To study the role of the mutations of p53, APC and K-ras genes in 47 cases of 3 types of intestinal metaplasia (IM) of gastric mucosa. Methods:In 47 cases of IM, exons 5- 8 of p53 and exons 15 of APC were examined with PCR-SSCP and codon 12 of K-ras with PCR-RFLP to detect the existence of any mutations of these structures. Results:Muta- tions of p53, APC and K-ras were found in 29.8% (14/47),6.4% (3/47) and 6.4% (3/47) respectively in our series of patients who consisted of 33 with types I and II and 14 with type III of IM. The mutation rate of p53 was far higher in patients with type III IM (57.1%,8/14) than in those with types I and II IM(18.2%,6/33)(P <0.05). Though the mutation rate of APC and K-ras was also higher in the patients with type III IM than in those with types I and II IM, it was of no statistical significance (P >0.05). In one case of type III IM, mutation of both p53 and K-ras was found. Conclusion: The molecular changes of 3 types of IM are different. The mutation of p53 may be closely related to carcinogenesis in cases of type III IM and it serve as a sign for the early diagnosis of gastric carcinoma.

Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury

Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.

Preliminary Investigation on Regulating Effects of Different TCM Treatments on Transcription of the Correlated Genes of Liver Cancer in Rats

The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcription were observed in the liver cancer model rats.The preliminary results indicated that the mRNA levels of H-ras N-ras and K-ras,and signal molecules correlated with the ras/MAPK signal transduction pathway were down-regulated by the different TCM treatments in varying degrees.Also,the regulating effects of the treatments on differently-displayed genes were discrepant.It is suggested that the molecular mechanisms of the TCM treatments for liver cancer was complex with different target genes.

Correlation between IL-1β,IL-1Ra gene polymorphism and occurrence of polycystic ovary syndrome infertility

Objective:To explore the relationship between IL-1β.IL-1Ra gene polymorphism and the occurrence of polycystic ovary syndrome(PCOS) infertility.Methods:A total of 59 PCOS infertility cases visiling the reproductive center of our hospital from Mar.2010 to Mar.2012 and 56 healthy women were selected.ELISA method was used lor the detection of IL-1β.IL-1Ra lewis,and the levels of serum supersensitivity C reaction protein(US-CRP).insulin(FINS),follieule-stimulating hormone(FSH) and fasting blood—glucose(FRG) were detected.PCR analysis technology was adopted to detect the gene polymorphism of the.511 site of IL-1βand the second introne of IL- 1Ra.Results:The levels of IL-1β.IL-1Ra.US-CRP.FINS and FBG in blood scrum of patients in PCOS group were significantly higher than those in control group(P【0.05 or P【0.01).The level of FSH in PCOS group was significantly lower than that in control group(P【0.05).The genotypic frequency of T/T.the 511 site of IL-1βin PCOS group was 42.37%.significantly higher than 1250%in control group 【P【0.01).The frequency of T allele was also significantly higher than that in control group(P【0.01).The genotypic frequency ofⅠ/Ⅴ.the second introne of IL-1Ra in PCOS group was 20.34%,signicianlly higher than 3.57%in control group(P【0.05).The frequency of V allele in PCOS group was significantly higher than that in control group(P【0.05).Conclusions: T allele of the 511 site of IL-1βgene and V allele of the second inlrone of IL-1Ra gene might be the genetic basis of the rising of IL-1β.IL-1Ra and US-CRP levels in blood serum of PCOS patients,and are associated with the infertility occurrence of PCOS patients.

Detecting K-ras and p53 gene mutation from stool and pancreatic juice for diagnosis of early pancreatic cancer

OBJECTIVE: To explore new methods for the early diagnosis of pancreatic cancer through detection of K-ras and p53 mutations in pancreatic juice and stool. METHODS: 201 patients in PUMC Hospital from 1994 - 2000 and 60 control individuals were enrolled in this study. K-ras point mutation was detected by PCR-RFLP while p53 mutation was detected by PCR-SSCP. RESULTS: K-ras mutation was found in pancreatic juice in 87.8% (36/41) of pancreatic cancer patients and 23.5% (4/17) of benign pancreatic disease patients. In 261 stool specimens, amplification found mutations successfully in 235 patients (90%). K-ras mutation was found in stool in 88% (66/75) of pancreatic cancer patients, 51.1% (24/47) of benign pancreatic disease patients and 19.6% (9/46) of normal individuals. p53 mutation was found in pancreatic juice in 47.4% (18/38) of pancreatic cancer patients and 12.5% (2/16) of benign pancreatic disease patients. p53 mutation was found in stool in 37.1% (23/62) and 19.1% (4/21) of chronic pancreatitis patients. CONCLUSION: K-ras mutation in pancreatic juice has higher diagnosis sensitivity and specificity, and therefore may be used as a supplement in the diagnosis of pancreatic cancer. Detection of K-ras mutation combined with p53 mutation in stool can aid in the screening of pancreatic cancer.

Inhibitary effects of antisense oligonucleotide specific to K-ras point mutation on the target gene expression in human pancreatic carcinoma cells

The prognosis of pancreatic carcinoma is disappointing due to the difficulty of early and accurate diagnosis,low operative resection rate, insensitivity to radiation therapy and chemotherapy. The incidence of pancreatic carcinoma has increased considerably in the past few years, the progress of diagnosis and treatment, however, has not been significantly improved. The overall 5-year survive rate is still as low as 5%-10%, and the improved 5 years survive rate is about 20%-40% after successive Whipple-operation. The early diagnosis is critical to the successful surgical treatment. It depends on the establishment of the new way for that.

Evaluation of Intraductal Ultrasonography, Endoscopic Brush Cytology and K-ras, P53 Gene Mutation in the Early Diagnosis of Malignant Bile Duct Stricture

Background： In qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. The aim of this study was to evaluate the value of intraductal ultrasonography （IDUS）, endoscopic brush cytology and K-ras, P53 gene mutation in the early diagnosis of malignant biliary stricture. Methods： From February 2012 to February 2013, 84 patients with suspected malignant biliary stricture were performed I DUS firstly, then endoscopic brush cytology and finally K-ras, P53 gene mutation detection, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of all above ways were evaluated and compared. Results： Of 84 patients, 52 cases were ultimately diagnosed malignant biliary stenosis; of which, 9 cases had no recurrence or metastasis to other organs after radical operation during the follow-up period. IDUS combined with brush cytology and K-ras ＋ P53 gene mutation detection had obvious advantage in the sensitivity, accuracy and negative predictive value than any other joint detection and single detection （the advantage was more significant compared with IDUS ＋ brush cytology or any single detection P 〈 0.01）. There were obvious statistical significance in the sensitivity and accuracy between IDUS ＋ brush cytology ＋ P53 or IDUS ＋ brush cytology ＋ K-ras and IDUS ＋ brush cytology or IDUS （P 〈 0.05）. There was no statistical significance in the sensitivity, specificity, positive predictive value, negative predictive value and accuracy between IDUS ＋ brush cytology ＋ P53 and IDUS ＋ brush cytology ＋ K-ras （P 〉 0.05）. Conclusions： IDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.

Association of Telomere DNA and c-Ras Gene Segment With Nuclear Matrix and Chromosome Scaffold

Nuclear matrix is a delicate proteineous network in eukaryote nucleus, and its functional diversity is becoming increasingly apparent.It is generally acknowledged that nuclear matrix,being a morphological and biochemical complex molecular

RAS基因相关性自身免疫淋巴增殖性疾病1例并文献复习

目的探讨RAS基因相关自身免疫淋巴增殖性疾病(Ras-associated autoimmune lymphoproliferative disorders,RALD)的临床特征及诊疗方法。方法分析2019年本院诊治的1例RALD患者的临床资料,以基因NRAS、KRAS或RALD为检索词,检索PubMed、中国知网、万方数据库2000年1月—2023年11月RAS基因变异相关文献并进行复习。结果患者因“发现血小板减少1.5年,反复发热1.5月”收住院。查体:轻度贫血貌,腹部膨隆,肝脏肋下5 cm,质韧,脾脏肋下3 cm。CD4-CD8-细胞的比例占淋巴细胞的2.3%。NK细胞脱颗粒功能下降。基因检测:存在NRAS基因2号外显子c.38G>A、p.G13D体细胞突变。共检索到RALD患者32例,其中NRAS基因体细胞突变致RALD有13例,KRAS基因体细胞突变致RALD有19例。32例RALD患者主要特征包括脾脏肿大,免疫性贫血,血小板减少,高丙种球蛋白血症,单核细胞增多,双阴性T细胞比例正常或轻度升高。结论RALD患者的临床特征为肝脾肿大、存在自身免疫现象等,基因分析有助于该疾病的诊断。

结直肠癌患者RAS、BRAF基因突变与MSI状态的相关性及其临床病理特征

目的:结直肠癌是人类最常见的恶行肿瘤之一,其发病率和病死率呈逐年上升趋势。本研究旨在分析结直肠癌患者大鼠肉瘤病毒癌基因(rat sarcoma viral oncogene,RAS)、鼠类肉瘤病毒癌基因同源物(V-Raf murine sarcoma viral oncogene homolog B,BRAF)突变与微卫星不稳定(microsatellite instability,MSI)状态相关性及其临床病理特征,为结直肠癌临床治疗及预后评估提供依据。方法:回顾性分析444例结直肠癌患者的临床病理资料,并提取肿瘤组织基因组DNA,采用荧光定量PCR法检测Kirsten大鼠肉瘤病毒癌基因同源物(Kirsten rat sarcoma viral oncogene homolog,KRAS)、Neuroblastoma大鼠肉瘤病毒癌基因同源物(neuroblastoma rat sarcoma viral oncogene homolog,NRAS)第2、3、4外显子及BRAF V600E突变;运用PCR-毛细血管电泳行MSI状态分析。结果:K(N)RAS基因突变184例(41.44%,184/444),其中KRAS突变173例(94.02%,173/184),NRAS突变11例(5.98%,11/184),K(N)RAS共突变3例。BRAF V600E突变21例(4.7%,21/444)。微卫星高度不稳定(microsatellite instability high,MSIH)48例(10.81%,48/444),微卫星低度不稳定(microsatellite instability low,MSI-L)和微卫星稳定(microsatellite stable,MSS)共396例(89.19%,396/444)。K(N)RAS基因突变右半结肠癌多于左半结肠癌,且黏液腺癌突变率高于单纯腺癌(均P<0.05)。K(N)RAS基因突变与患者性别、年龄、肿瘤大小、肉眼分型、组织学分化程度、淋巴结转移、病理分期均无关(均P>0.05)。女性BRAF V600E突变高于男性,低分化高于中分化(均P<0.05),BRAF V600E突变与患者发病年龄、肿瘤位置、大小、肉眼分型、组织学类型、淋巴结转移、病理分期均无关(均P>0.05)。发生MSI-H的患者中,右半结肠癌多于左半结肠癌,肿瘤直径≥4.5 cm病例多于直径更小病例,隆起型多于其他肉眼分型,黏液腺癌多于单纯腺癌,低分化多于高分化(均P<0.05),而与患者性别和年龄均无关(均P>0.05)。K(N)RAS突变与MSI-H发生无关(P>0.05),但RAS基因Gly位点突变与MSI-H发生相关(P<0.05)。携带RAS基因Gly位点突变的MSI-H结直肠癌患者男性多于女性,发病年龄无差异,右半结肠多于左半结肠,肉眼分型多为溃疡型,单纯腺癌比例高于黏液腺癌,多为中低分化,较多处于病理分期I~II期,常不伴淋巴结转移和BRAF V600E突变,Gly突变位点多为Gly12Ser/Asp突变。BRAF V600E突变与MSI-H发生有关(P<0.05)。与K(N)RAS突变型MSI-L/MSS结直肠癌比较,K(N)RAS突变型MSI-H结直肠癌较易发生于右半结肠,肿瘤直径≥4.5 cm的病例较多,组织学类型多为黏液腺癌,较少发生淋巴结转移,多处于病理分期I~II(均P<0.05);K(N)RAS突变型MSI-H结直肠癌与性别、年龄、肿瘤肉眼分型、组织学分化均无相关(均P>0.05)。与RAS野生型-MSI-L/MSS结直肠癌比较,RAS野生型-MSI-H结直肠癌多发生于右半结肠,肿瘤直径≥4.5 cm,多为溃疡型和隆起型,较多为黏液腺癌,且多为中低分化(均P<0.05),而RAS野生型-MSI-H结直肠癌与性别、年龄、淋巴结转移、病理分期均无关(均P>0.05)。结论:结直肠癌KRAS基因Gly位点突变、BRAF V600E突变与MSI-H发生相关;MSI-H-RAS基因Gly点突变结直肠癌患者有其独特的临床病理特征;RAS-MSI基因状态与临床病理特征相关;K(N)RAS、BRAF V600E、MSI检测有利于结直肠癌患者个体化治疗及预后评估。