Detection of RAS gene mutation and its clinical significance in children with acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia.@*METHODS@#A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children.@*RESULTS@#Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×109/L at diagnosis was worse (P<0.05).@*CONCLUSIONS@#RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis.

Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies

The Ras family of small Guanosine Triphosphate (GTP)-binding proteins (G proteins) represents one of the main components of intracellular signal transduction required for normal cardiac growth, but is also critically involved in the development of cardiac hypertrophy and heart failure. The present review provides an update on the role of the H-, K- and N-Ras genes and their related pathways in cardiac diseases. We focus on cardiac hypertrophy and heart failure, where Ras has been studied the most. We also review other cardiac diseases, like genetic disorders related to Ras. The scope of the review extends from fundamental concepts to therapeutic applications. Although the three Ras genes have a nearly identical primary structure, there are important functional differences between them: H-Ras mainly regulates cardiomyocyte size, whereas K-Ras regulates cardiomyocyte proliferation. N-Ras is the least studied in cardiac cells and is less associated to cardiac defects. Clinically, oncogenic H-Ras causes Costello syndrome and facio-cutaneous-skeletal syndromes with hypertrophic cardiomyopathy and arrhythmias. On the other hand, oncogenic K-Ras and alterations of other genes of the Ras-Mitogen-Activated Protein Kinase (MAPK) pathway, like Raf, cause Noonan syndrome and cardio-facio-cutaneous syndromes characterized by cardiac hypertrophy and septal defects. We further review the modulation by Ras of key signaling pathways in the cardiomyocyte, including: (i) the classical Ras-Raf-MAPK pathway, which leads to a more physiological form of cardiac hypertrophy; as well as other pathways associated with pathological cardiac hypertrophy, like (ii) The SAPK (stress activated protein kinase) pathways p38 and JNK; and (iii) The alternative pathway Raf-Calcineurin-Nuclear Factor of Activated T cells (NFAT). Genetic alterations of Ras isoforms or of genes in the Ras-MAPK pathway result in Ras-opathies, conditions frequently associated with cardiac hypertrophy or septal defects among other cardiac diseases. Several studies underline the potential role of H- and K-Ras as a hinge between physiological and pathological cardiac hypertrophy, and as potential therapeutic targets in cardiac hypertrophy and failure. Highlights - The Ras (Rat Sarcoma) gene family is a group of small G proteins - Ras is regulated by growth factors and neurohormones affecting cardiomyocyte growth and hypertrophy - Ras directly affects cardiomyocyte physiological and pathological hypertrophy - Genetic alterations of Ras and its pathways result in various cardiac phenotypes? - Ras and its pathway are differentially regulated in acquired heart disease - Ras modulation is a promising therapeutic target in various cardiac conditions.

Impact of mutant RAS on prognosis of patients after hepatic resection for colorectal cancer liver metastases / 中华肝胆外科杂志

Objective To study the impact of RAS status on prognosis of patients after liver resection for colorectal cancer liver metastases (CRLM).Methods The data of 545 consecutive CRLM patients who underwent liver resection at the Hepatopancreatobiliary Surgery Department I,Peking University Cancer Hospital between January 1st,2008 and December 31st,2016,were retrospectively reviewed.According to the inclusion and exclusion criteria,356 patients were eventually included into this study.There were 232 males and 124 females,with ages ranging from 21 to 83 years.The clinical and follow-up data of patients with wild-type and mutant RAS were compared.Survival was estimated by the Kaplan-Meier method,and the difference was compared by the log-rank test.Factors influencing survival of these patients were assessed by univariate and multivariate Cox regression analyses.Results There were 247 patients with wild-type RAS and 109 patients with mutant RAS,respectively.The median overall survival of patients with wild-type and mutant RAS were 74 and 30 months respectively.Compared with mutant RAS patients,wild-type RAS patients had significantly better cumulative survival and disease free survival rates (both P ＜ 0.05).Multivariate Cox regression analyses revealed disease free interval from primary to metastases ≤ 12 months (HR =1.673,95％ CI:1.016-2.637),largest hepatic tumor diameter ＞ 5 cm (HR =1.717,95 ％ CI:1.102-2.637),and mutant RAS (HR =1.836,95％ CI:1.322-2.550) were independent risk factors for patients with colorectal cancer liver metastases after hepatic resection.Conclusion Mutant RAS was a poor prognostic factor of survival after liver resection in CRLM patients

Significance of K-ras gene status and ras protein expression in immunophenotypic classification of gastric signet ring cell carcinoma / 重庆医学

Objective To investigate the significance of K-ras gene status and ras protein expression in immunophenotypic classification of gastric signet ring cell carcinoma.Methods The expression of ras protein in 180 cases of gastric signet-ring cell carcinoma was detected by tissue microarray immunohistochemistry.Meanwhile,the mutation in codon 12,13 of K-ras gene was determined by using PCR-based DNA direct sequencing analysis.Results The rate of ras protein expression was 27.8％.The rate of ras protein expression in intestinal phenotype was significantly higher than those in gastric and gastrointestinal phenotypes(P<0.05).The rate of ras protein expression in cases with lymph node metastasis was significantly higher than those in cases without nodal involvement(P<0.05).The rate of ras protein expression was significantly higher in cases with deeper invasion(P<0.05).The frequency of K-ras gene mutation was 22(12.2％).All of them were found in codon 12.The types of mutation included GGT→AGT(1 case),GGT→TGT(1 case),GGT→GCT(2 cases),GGT→GTT(8 cases)and GGT→GAT(10 cases).K-ras mutation was significantly associated with intestinal phenotype(P<0.05).The rates of ras protein expression in cases with mutational type of K-ras gene was higher than those in cases with wild type(P<0.05).The ras protein expression was positively associated with K-ras gene mutation(r=0.61,P<0.05).Conclusion The ras protein expression is correlated with nodal involvement and invasion.K-ras gene mutation and expression of ras protein is related to phenotypic classification,and they might influence the phenotypic transformation in gastric signet ring cell carcinoma.

Relevant research of PD-1, PD-L1 protein expression and K-RAS gene mutations in lung adenocarcinoma / 临床与实验病理学杂志

Purpose To investigate the association of the PD-1 and PD-L1 protein expression with K-RAS gene mutations in lung adenocarcinoma.Methods The protein expression of PD-1 and PD-L1 was detected by immunohistochemical EnVision two-step staining,the K-RAS mutation was examined by realtime fluorescent quantitative PCR.Results The positive rate of PD-1 and PD-L1 was higher in lung adenocarcinoma than benign lung disease (P ＜ 0.01).There was no relationship between PD-1 and PD-L1 protein expression with the gender,age,smoking condition,differentiation,lymph node metastasis and TNM stages (P ＞ 0.05).The K-RAS gene mutations were detectable in 8 patients (22.2％) among 36 lung adenocarcinoma,there was no association between K-RAS gene mutation with the gender,age,smoking condition,differentiation,lymph node metastasis and TNM stages (P ＞ 0.05).The correction analysis showed that there was no relationship between PD-1 and PD-L1 protein expression with K-RAS mutation (P ＞ 0.05).Conclusion The positive rate of PD-1 and PD-L1 is higher in lung adenocarcinoma than benign lung disease,but there is no relationship among PD-1 and PD-L1 protein expression with its clinal pathological characteristics and K-RAS mutation in lung adenocarcinoma.

Correlation of RAS mutations and microsatellite instability with clinico-pathological features and prognosis of patients with stage Ⅲ colorectal cancer / 中国病理生理杂志

AIM:To investigate the status of RAS/BRAF mutations and microsatellite instability ( MSI ) and their associations with clinicopathological features and prognosis of the patients with stage Ⅲ colorectal cancer ( CRC ) . METHODS:The surgical patients with stage ⅢCRC (n=281) were followed up.The mutations of RAS/BRAF were ex-amined by PCR amplification-Sanger sequencing , and MSI status was detected using immunohistochemistry ( IHC) in their archival paraffin-embedded tissue specimens .The relationships of the status with the clinicopathological features and prog-nosis of the patients were statistically analyzed .RESULTS: Among 281 patients, the mutations of RAS/BRAF were ob-served in 136 cases (48.4%), including 116 cases (41.3%) of KRAS mutations.RAS/BRAF mutations were highly cor-related with the level of carcino-embryonic antigen (P<0.05).Moreover, 18 cases (6.4%) of MSI-high (MSI-H) pa-tients were determined by IHC, and MSI-H status was more common in N2b patients (P<0.05).Correlation study found that the mutation rate of BRAF was higher in MSI-H tumors than that in MSI-low ( MSI-L)/microsatellite stability ( MSS) counterparts (P<0.01), although no association between KRAS/NRAS mutations and the MSI status was observed .The prognosis in the patients with wild-type RAS/BRAF or MSI-H was better than the patients with any mutation or MSI-L/MSS (P<0.01).CONCLUSION:Mutant RAS/BRAF and MSI may serve as fairly good indicators for prognosis of the patients with stage Ⅲ CRC.

Correlation of RAS mutations and microsatellite instability with clinico-pathological features and prognosis of patients with stage Ⅲ colorectal cancer / 中国病理生理杂志

AIM:To investigate the status of RAS/BRAF mutations and microsatellite instability ( MSI ) and their associations with clinicopathological features and prognosis of the patients with stage Ⅲ colorectal cancer ( CRC ) . METHODS:The surgical patients with stage ⅢCRC (n=281) were followed up.The mutations of RAS/BRAF were ex-amined by PCR amplification-Sanger sequencing , and MSI status was detected using immunohistochemistry ( IHC) in their archival paraffin-embedded tissue specimens .The relationships of the status with the clinicopathological features and prog-nosis of the patients were statistically analyzed .RESULTS: Among 281 patients, the mutations of RAS/BRAF were ob-served in 136 cases (48.4%), including 116 cases (41.3%) of KRAS mutations.RAS/BRAF mutations were highly cor-related with the level of carcino-embryonic antigen (P<0.05).Moreover, 18 cases (6.4%) of MSI-high (MSI-H) pa-tients were determined by IHC, and MSI-H status was more common in N2b patients (P<0.05).Correlation study found that the mutation rate of BRAF was higher in MSI-H tumors than that in MSI-low ( MSI-L)/microsatellite stability ( MSS) counterparts (P<0.01), although no association between KRAS/NRAS mutations and the MSI status was observed .The prognosis in the patients with wild-type RAS/BRAF or MSI-H was better than the patients with any mutation or MSI-L/MSS (P<0.01).CONCLUSION:Mutant RAS/BRAF and MSI may serve as fairly good indicators for prognosis of the patients with stage Ⅲ CRC.

Using next-generation sequencing technology to evaluate biomarkers associated with anti-EGFR efficacy in metastatic colorectal cancer / 中国肿瘤临床

Objective:To explore genes associated with sensitivity to anti-EGFR therapy. Methods:From March 2012 to August 2013, 31 metastatic colorectal cancer patients in Peking University Cancer Hospital&Institute were treated with anti-EGFR mono-therapy. A total of 21 genes associated with oncogenesis, metastasis, and EGFR signaling pathway were profiled in these 31 patients by using tar-geted next-generation sequencing technology. Results:A total of 31 patients with Kras exon 2 wild-type received anti-EGFR therapy as third-line treatment. Among these patients, the median progression-free survival (PFS) was 89 days, overall survival was 311 days, and objective response rate was 16.1%. Five cases harbored Kras exons 3/4 or Nras exons 2/3 mutations. These five Ras mutation patients showed disease progression during the first evaluation with 31-day PFS. One PIK3CA mutation case exhibited disease progression dur-ing the first evaluation (PFS 35 days), and one case showed mTOR mutation with 91-day PFS. The PFS of two cases with SMAD4 muta-tion were 58 and 59 days, whereas that of the case containing FBXW7 mutation was 93 days. Among the 26 Ras wild-type patients, MLL3, TP53, and APC were the three genes with the highest mutation frequencies of 92.3%(24/26), 53.8%(14/26), and 42.3%(11/26), respectively. Conclusion:Extended Ras analysis (including Kras and Nras exons 2/3/4) is recommended for patients who are candi-dates for anti-EGFR therapy. Mutations in the downstream effectors of the EGFR signaling pathway, such as PI3KCA and mTOR, may al-so have a predictive role in anti-EGFR therapy. Mutations beyond the EGFR pathway such as FBXW7 and SMAD4 may be associated with anti-EGFR efficacy and deserve further attention.

High-resolution melting analysis for detection of K-ras mutation in colorectal cancer and its clinical significance / 医学研究生学报

Objective The K-ras gene plays a major role in the development , progression, and drug selection for the target treatment of colorectal cancer .The aim of this study was to evaluate the feasibility of detecting K-ras mutation in colorectal cancer by high-resolution melting ( HRM) analysis and to investigate the relationship between K-ras mutation and the clinicopathological parame-ters of colorectal cancer. Methods We collected the tissue samples of colorectal cancer from 179 patients, detected the mutations in codons 12 and 13 of the K-ras gene, and analyzed the relationship between K-ras mutation and the clinicopathological parameters of the patients. Results In the 179 cases of colorectal cancer, K-ras mutation was found in 77 (43.02%), significantly higher in those aged ≥60 years than in those aged <60 years (55.17% vs 33.70%, P<0.05).Multivariate logistic regression analysis showed a significant influence of age on K-ras mutation (OR=1.506, 95%CI:1.028-2.011, P<0.05). Conclusion HRM analysis is a rapid, sensitive, and inexpensive diagnostic tool for the detection of K-ras mutation, and K-ras mutation is associated with the age of colorectal cancer patients .

Characterization of growth performance of F1 hybrid CB6 F1 C57-ras transgenic mouse model / 中国比较医学杂志

Objective To obtain the basic growth parameters of a self-established F1 hybrid CB6F1 C57-ras transgenic mouse model, and to provide basic information for commercialization of this mouse model. Methods F1 hybrid mice (CB6F1) were produced by crossing C57-ras heterozygous transgenic (c-Ha-ras+/-) male mice and wild-type BALB/cJ female mice.The average litter size, weaning rate, sex ratio, growth performance and C57-ras transgenic positive rate were recorded and analyzed.Results The average litter size was eight, weaning rate was 90%, and sex ratio was approximately in accordance with prediction.The average body weight of newborn mice was 1.73 ±0.05 g.The average body weight of 10-week old c-Ha-ras transgenic female and male mice in CB6F1 background was 24.38 ±1.74 g and 29.42 ±1.72g, respectively, which had a significant difference (P<0.01).The c-Ha-ras transgenic positive rate was 46.9%. which was in accordance with genetic rules.Conclusions The F1 hybrid mice (CB6F1) produced by crossing C57-ras heterozygous transgenic ( c-Ha-ras +/-) male mice and wild-type BALB/cJ female mice show normal growth performance and development characteristics, and it can be used for large-scale commercial supply.

Identification of cut off value and lower limit of detection for K-ras mutation by PNA-PCR clamping method / 中华胰腺病杂志

Objective To determine the lower limit of detection (LLOD) and cut off values of K-ras mutation detection by peptide nucleic acid (PNA) clamping-PCR.Methods The genomic DNA of pancreatic cancer cell lines (PANC1 and SW1990) with codonl2,13 mutation and the genomic DNA of placenta with K-ras wild type were mixed and diluted serially into samples with different mutation rate (0,0.1％,0.2％,0.4％,0.8％,1.6％,3.1％,6.25％,12.5％,25％,50％),PANC1 cells with 1％ mutation rate and SW1990 cells with 30％ mutation rate and 4 samples with the quantity of DNA was 50,20,5,1 ng and 50,10,5,1 ng was prepared.Codon 12,13 mutation of K-ras was determined by PNA-PCR,and the mutation Ct values,overall Ct values were collected,and the △Ct values (mutation Ct values-overall Ct values) were calculated,and the tests were repeated for 10 times.ROC curve was used to analyze the △Ct values and determine the best cut off values for K-ras mutation,and the positive diagnostic rate,LLOD was evaluated.Results The mutation Ct,△Ct values of codon 12 mutation of PANC1 and codon 13 mutation of SW1990 of all the different mutation rates were statistically significantly different (P ＜ 0.05) when compared with negative control group,but the overall Ct values were not statistically significantly different from that of negative control group.For detection of K-ras codon 12 mutation by ROC curve,the relevant area of ROC curve (AUC) was 0.926,the optimum cut off value of △CT was 11,the sensitivity and specificity were 84％ and 100％,respectively,and the LLOD was 0.4 ng.For detection of K-ras codon 13 mutation by ROC curve,the relevant AUC was 0.906,the optimum cut off value of △CT was 9.5,the sensitivity and specificity were 71％ and 100％,respectively,and the LLOD was 1.5 ng.The mutation detection results of fixed rate further confirmed the LLOD.Conclusions This study successfully defines LLOD and cut off value of PNA clamping-PCR/K-ras method in detection of K-ras 12 and 13 codon mutations.This method meets the requirement of clinical application.

Effect of cetuximab chemotherapy on operation resection rate of wild type k-ras gene in liver metastasis of colorectal cancer / 中国基层医药

Objective To explore the clinical effect and safety of cetuximab plus mFOLFOX6 first-line treatment in k-ras wild type patients with liver metastasis from colorectal cancer.Methods 40 k-ras wild-type colorectal cancer patients with liver metastasis diagnosed by histological detection in our hospital were chosen.20 patients in the observation group were treated with cetuximab plus mFOLFOX6.20 patients in the control group were only given mFOLFOX6.To observe the effect and safety of the two groups.Results RR,operation excision rate and R0 removal rate of observation group (60％,45％,35％) were significantly higher than those of the control group (30％,15％,10％),the differences were statistically significant (x2 =3.95,4.36,4.28,P ＜ 0.05);The PFS of the observation group (16.37 ± 7.24) was higher than (11.52 ± 6.85) in the control group,but the difference was not statistically significant (P ＞ 0.05).In the observation group,there were 2 cases with rash,2 cases of leukopenia,1 case with nausea and vomiting,the incidence rate of adverse reaction was 25 ％ (5/20) ;In the control group,there were 2cases with leukopenia,1 case with nausea and vomiting,there was no rash and paronychia,the incidence rate of adverse reaction was 15％ (3/20),there was no significant difference in incidence rate of adverse reaction between the two groups (P ＞ 0.05).Conclusion Cetuximab combined with FOLFOX6 can improve the performance clinical remission rate and lesion resection rate of k-ras wild type patients with liver metastases from colorectal cancer,and has high safety,which is worthy of clinical application.

Roles of K-ras gene in non-small cell lung cancer / 国际肿瘤学杂志

K-ras gene is one of oncogenes in non-small cell lung cancer,and it can promote tumor cells growth after mutations by several signaling pathways.K-ras mutations frequently occur in lung adenocarcinoma patients with smoking history.In the present study,K-ras mutations are associated with resistence to targated therapy and may be a marker of poor prognosis in patients with non-small cell lung cancer.

K-ras gene and colorectal cancer therapeutic effect / 国际肿瘤学杂志

K-ras gene is one of oncogenes,which promotes cells growth and differentiation.Ras protein loses the activity of GTP enzyme because of K-ras mutations,and that may cause abnormal growth,differentiation of cells and promote the occurrence of tumor.Patients with colorectal carcinoma that carry mutations in K-ras gene do not benefit from the administration of anti-epidermal growth factor receptor (EGFR) polyclonal antibodies.Different solid tumors of colorectal carcinoma have different K-ras mutation rates.Different genotypes of K-ras gene (wild-type or K-ras mutant type) affect significantly on treatment options and prognosis.The efficacy of mutant type patients with anti-EGFR antibodies is poor,and the therapeutic effects of 5-FU and FOLFOX are still unclear.

Detection of K-ras mutation by PNA-PCR/K-ras method in diagnosis of colorectal cancer tissues / 第二军医大学学报

Objective To determine the positive judgement standard of K-ras mutation detection method peptide nucleic acid (PNA)-PCR/K-ras (previously established in our laboratory) and to assess its diagnostic value for colorectal cancer tissues. Methods Plasmidswith K-ras codon 12 mutation and plasmids with K-ras wild-type plasmids were mixed and serially diluted into standard samples (mutation/total: 0, 1/3 200, 1/1 600, 1/800, 1/400, 1/200, 1/100) for six independent tests. The mutation CT, total CT and ΔCT (mutation CT-total CT) values were obtained by PNA-PCR/K-ras method. After the cut-off values of the mutation CT and ΔCT for K-ras diagnosis were identified by ROC analysis, the diagnostic criteria for K-ras mutation was defined by combining both the cut-off values of the mutation CT and ΔCT. A comparison was made between K-ras diagnostic rate by PNA-PCR/K-ns method and direct sequencing for 35 colorectal cancer tissues and their corresponding adjacent noncancerous tissues. Results The mutation CT and ΔCT values for 1/800 and the above standard samples were significantly different from those of the negative samples(P<0. 05), with the optimumcut-off values of mutation CT and ΔCT being 41. 7 and 15. 4, respectively. The diagnostic criteria (mutation CT≤41. 7 or ΔCT≤15. 4) for K-ras mutation was set up asAUC-ROC 0. 955 (P=0. 001). According this diagnostic criteria, the K-ras mutation diagnostic rates in each concentration gradient of the standard samples (0, 1/3 200, 1/1 600, 1/800, 1/400, 1/200, and 1/100) were 0%,66.7%,83.3%,100%, 100%, 100%,and 100%, receptivity, with the upper diagnostic limit being 1/800. The diagnostic rates of K-ras mutation by our method and by direct sequence method for colorectal cancer tissues were 45. 7% (32/70) and 18. 6% (13/70), respectively, showing significant difference (P = 0. 000). Conclusion PNA-PCR/K- ras method has higher sensitivity and positive detection rate than direct sequencing method for colorectal cancer tissues.

Evaluation of K-ras status concordance between primary colorectal cancer and related metastatic sites / 中国癌症杂志

Background and purpose:Metastatic colorectal cancer (mCRC) patients with K-ras mutation won’t benefit in the anti-epidermal growth factor receptor (EGFR) treatments. Thus K-ras mutation analysis is mandatory before this treatment. There is controversy that K-ras mutation analysis should be performed on primaries or related metastases. The aim of our study was to evaluate the concordance of K-ras status between primary and related metastases tumors, thus investigate the validity and rigorousness of clinical K-ras testing. Methods:Seventy-six patients with confirmed mCRC treated in Fudan University Shanghai Cancer Center were enrolled. After DNA extraction and PCR amplification, tumor specimens with paired primary tumors and related metastatic sites were put into sequencing analysis. And the K-ras mutation status in exon 2 was assessed. Results: K-ras mutation was detected in 31 out of 76 primary tumours (40.8%) and also 40.8%of the metastatic sites. But discordance was found between primary tumor and metastasis in 15 cases (19.7%):8 primary tumors had a K-ras mutation with a wild-type metastasis, meanwhile 7 primary tumors were wild type with a K-ras-mutated metastasis. Conclusion:Our study indicated that quite a few mCRC cases have different K-ras status between primary tumors and related metastatic sites, and it’s not very rigorous to choose the anti-EGFR treatments merely according to the primary tumor-K-ras mutation.Further study and consultation are needed on this problem.

K-ras gene mutation in clinical diagnosis and risk factors of pancreatic cancer: A review / 第二军医大学学报

The early symptoms and laboratory findings of pancreatic cancer are nonspecific and the outcome of victims are poor. Currently surgical resection is the only means for cure. When pancreatic cancer is clinically suspected, it is usually non-resectable due to metastasis. So prevention and early diagnosis are especially important for pancreatic cancer. The risk factors of pancreatic cancer include male sex, old age, long-term smoking, coffee consumption, alcohol abuse, diabetes, chronic pancreatitis, hereditary factors, obesity, non-familial hypercholesterolemia, high caloric intake, and environmental factors. Many studies have indicated that pancreatic cancer is closely related to K-ras mutations, and patients with high susceptibility have a higher probability of K-ras mutations. This paper reviews the value of K-ras mutation in diagnosis of pancreatic cancer, K-ras mutation in pre-cancerous lesions, and the relation between high-risk factors and K-ras mutations.

Significance of quantitatively detecting K-ras codon 12 and 13 mutations in the tissues of pancreatic cancer and related pancreatic diseases / 中华胰腺病杂志

ObjectiveTo investigate the clinical significance of quantitative detection of K-ras codon 12 and 13 mutations in the tissues of pancreatic cancer and related pancreatic diseaaes. Methods One hundred and thirty samples from surgically removed pancreatic tissue with a conclusive pathological diagnosis (105 cases of pancreatic ductal adenocarcinoma,8 cases of pancreatic adenosquamous carcinoma of the pancreas,2 cases of pancreatic mucinous adenocarcinoma,3 cases of pancreatic endocrine carcinoma,6 cases of duodenal and papillary adenocarcinoma and 6 cases of benign pancreatic diseases ) were collected.Quantitative detection of K-ras codon 12 and 13 mutations was performed by the method of peptide nucleic acidmediated PCR clamping with two different fluorescence labeled probes.Mutation number ＞ 100 copies was used as the criteria to calculate the positive mutation rate.ResultsThe median and quartile of K-ras codon 12mutations of pancreatic ductal adenocarcinoma,adenosquamous carcinoma of the pancreas,pancreatic mucinous adenocarcinoma,pancreatic endocrine carcinoma,duodenal and papillary adenocarcinoma and benign pancreatic diseases were 4062 (495,10800),238 (45,8420),15 (9,21),3 (3,16),2283 (73,5037)and 21(8,56),and the positive mutation rates were 84.8％ (89/105),50.0％ (4/8),0,0,66.7％ (4/6)and 16.7％ (1/6).The quantity of K-ras codon 12 mutation in pancreatic ductal adenocarcinoma was not statistically different from those of adenosquamous carcinoma,duodenal and papillary adenocarcinoma,but it was significantly higher than those in pancreatic mucinous adenocarcinoma,pancreatic endocrine carcinoma,and benign pancreatic diseases (P ＜0.05).The area under ROC of K-ras codon 12 mutation in pancreatic ductal adenocarcinoma was 0.727.The sensitivity and specificity of the K-ras codon 12 mutation for the diagnosis of pancreatic ductal adenocarcinoma were 84.8％,64.0％,respectively.The quantity of K-ras codon 12 was associated with survival of patients with pancreatic ductal adenocarcinoma.The quantity of K-ras codon 13 mutations and the positive mutation rates in pancreatic ductal adenocarcinoma was not statistically different from other pancreatic diseases.ConclusionsThe quantity of K-ras codon 12 mutation has good differential diagnostic and prognostic prediction value for pancreatic ductal adenocarcinoma.

Role of K-ras gene mutations in carcinogenesis, diagnosis and treatment of patients with lung adenocarcinoma / 第二军医大学学报

K-ras gene mutalion iscommonly seen in lung adenocarcinoma. Cigarette smoking is thought to be an important reason for K-ras gene mutation. Studies have repotted that K-ras mutations can influence the subtyping and prognosis of lung adenocarcinoma. Recently, the techniques to detect K-ras mutation have been continuously improved, greatly promoting the detection sensitivity of K-ras mutations, even in tissues with small amount of tumor component. Emerging data showed that K-ras mutation can induce primary resistance of lung adenocarcinoma to tyrosine kinase inhibitors (TKIs) and decrease the efficacy of chemotherapy. Therefore, K-ras mutation has attracted considerable attention as a target for diagnosis and anticancer therapy. In this review, we summarize recent studies on K-ras mutations in lung adenocarcinoma, and discuss the development, diagnosis, and treatment of lung adenocarcinoma.

Effect of N-Ras by RNA interference on radiosensitivity of hepatoma carcinoma cell MHCC97-H line / 中华放射医学与防护杂志

Objective To investigate the radiosensitivity of silencing N-Ras by RNA interference in hepatoma carcinoma cell MHCC-97.Methods N-Ras RNA interference (RNAi) vector was constructed by using pcDNA 6.2-GW/EmGFP-mir plamid.The RNAi effect was detected by RT-PCR,Western bolt,immunohistochemisty and MTT method.Survival curve for each cell line were obtained by measuring the clone forming abilities of irradiated cell populations.Results After silencing the N-Ras by RNAi,The expression level of N-Ras mRNA,N-Ras protein,immunohistochemisty were decreased 96.9% ±0.159%(t=40.377,P＜0.05),89.8%±0.012% (t=31.595,P＜0.05),90%,respectively,and The survival of hepatoma carcinoma cell MHCC-97 line were inhibited 21.9% (F = 4.63,P < 0.05).Which have significant difference in statistics.The SER of hepatoma carcinoma cell MHCC-97 line after interference was 1.15.Conclusions RNAi targeting silence N-Ras may increase the radiosensitivity of hepatoma carcinoma cell MHCC-97 line.