Rat Sarcoma Viral Oncogene Mutation Research Articles

Radiological and clinical features of large consolidative-type pulmonary invasive mucinous adenocarcinoma.

This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative-type pulmonary invasive mucinous adenocarcinomas (IMA). We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative-type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence-free survival (RFS) and overall survival (OS) were determined using the Kaplan-Meier method. Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread-through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4months, respectively, with 3-year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis. Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3-T4; however, lymph node metastasis was rare.

Kristen Rat Sarcoma Viral Oncogene Mutations in Colorectal Carcinomas at the University Teaching Hospital in Lusaka, Zambia

Background: The second leading cause of cancer-related deaths worldwide is colorectal cancer. With an incidence rate of 4.8 per 100,000, this is Zambia’s sixth most prevalent cancer;
 
 Methods: This laboratory-based, cross-sectional study examined the frequency of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation and its association with prognostic factors in colorectal carcinoma cases from the University Teaching Hospital-Adult Hospital (UTHs), Lusaka, Zambia;
 
 Results: Thirty (30) formalin-fixed paraffin-embedded (FFPE) samples collected between June 2017 and June 2018 were sent to the Lancet laboratories and analyzed for KRAS mutations (codons 12 and 13). One FFPE block did not meet the inclusion criteria and was excluded. The demographic and clinicopathological data were analyzed using STATA 12. Males outnumber females by 20 to nine. The average age of the patient was 45 ± 16 years. The rectum was the location of 44.8% of the tumors, with the majority being conventional adenocarcinoma (CAC) (65.6 %). All cases (100%) had advanced-stage (stages 3 and 4) disease; however, only 27.6% of patient tumors exhibited lymphovascular invasion. KRAS mutation was detected in 11 (37.9%) cases and mainly in left-sided tumors (62.5%). KRAS mutations were only detected in CAC and serrated adenocarcinoma subtypes. No significant associations were observed between the KRAS mutation status and tumor or patient’s clinical and sociodemographic factors;
 
 Conclusion: We advocate for incorporating KRAS mutation testing into the standard of care for treating colorectal cancer.

Kristen Rat Sarcoma Viral Oncogene Mutations in Colorectal Carcinomas at the University Teaching Hospital in Lusaka, Zambia

Background: The second leading cause of cancer-related deaths worldwide is colorectal cancer. With an incidence rate of 4.8 per 100,000, this is Zambia’s sixth most prevalent cancer;
 Methods: This laboratory-based, cross-sectional study examined the frequency of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation and its association with prognostic factors in colorectal carcinoma cases from the University Teaching Hospital-Adult Hospital (UTHs), Lusaka, Zambia;
 Results: Thirty (30) formalin-fixed paraffin-embedded (FFPE) samples collected between June 2017 and June 2018 were sent to the Lancet laboratories and analyzed for KRAS mutations (codons 12 and 13). One FFPE block did not meet the inclusion criteria and was excluded. The demographic and clinicopathological data were analyzed using STATA 12. Males outnumber females by 20 to nine. The average age of the patient was 45 ± 16 years. The rectum was the location of 44.8% of the tumors, with the majority being conventional adenocarcinoma (CAC) (65.6 %). All cases (100%) had advanced-stage (stages 3 and 4) disease; however, only 27.6% of patient tumors exhibited lymphovascular invasion. KRAS mutation was detected in 11 (37.9%) cases and mainly in left-sided tumors (62.5%). KRAS mutations were only detected in CAC and serrated adenocarcinoma subtypes. No significant associations were observed between the KRAS mutation status and tumor or patient’s clinical and sociodemographic factors; 
 Conclusion: We advocate for incorporating KRAS mutation testing into the standard of care for treating colorectal cancer.

79P Molecular characterization of KRAS NSCLC all stages: A single-center cohort

Kirsten rat sarcoma viral oncogene mutation (KRASm) is detected in approximately 25% of non-small cell lung cancer (NSCLC) adenocarcinoma patients (pts). As Next-generation sequencing (NGS) has been increasingly employed, diverse KRASm subtypes (subt) with different prognoses, incidences of co-mutations and characteristics have been described.

Single-Cell Digital Microfluidic Mass Spectrometry Platform for Efficient and Multiplex Genotyping of Circulating Tumor Cells.

Gene mutation profiling of heterogeneous circulating tumor cells (CTCs) offers comprehensive and real-time molecular information of tumors for targeted therapy guidance, but the lack of efficient and multiplex genotyping techniques for single-CTC analysis greatly hinders its development and clinical application. This paper reports a single-CTC mass spectrometry analysis method for efficient and multiplex mutation profiling based on digital microfluidics. Digital microfluidics affords integrated single-CTC manipulation, from single-CTC isolation to high-performance whole genome amplification, via nanoliter droplet-based wettability trapping and hydrodynamic adjustment of cell distribution. Coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, multiplex mutation information of individual CTCs can be efficiently and accurately identified by the inherent mass differences of different DNA sequences. This platform achieves Kirsten rat sarcoma viral oncogene mutation profiling of heterogeneous CTCs at the single-cell level from cancer patient samples, offering new avenues for genotype profiling of single CTCs and cancer therapy guidance.

KRAS Oncogene Mutations in Colorectal Cancer Patients in a Nepalese Tertiary Care Hospital.

Colorectal cancer is one of the most common cancers in the world and ranks among top ten cancer in Nepal. Limited data have been reported in the literature regarding the prevalence of Kristen Rat Sarcoma viral oncogene mutation in Nepalese patients with colorectal cancer. In a low income country such as Nepal where majority of cancer patient pay for treatment out-of-pocket, it is important to ascertain Kristen Rat Sarcoma viral oncogene mutation status before starting treatment with these agents. We analysed 22 colorectal cancer specimens diagnosed histopathologically. Real Time Polymerase Chain Reaction was performed on extracted DNA using RoterGene from Qiagen. US Food and Drug Administration approved kit was used for detection of Kristen Rat Sarcoma viral oncogene mutation i.e. TheraScreen: K-RAS Mutation Kit: The K-RAS Kit detects seven Kristen Rat Sarcoma viral oncogene mutations in codons 12 and 13 of the Kristen Rat Sarcoma viral oncogene. Kristen Rat Sarcoma viral oncogene mutation was observed in 13 (59%) of the samples studied. All samples had point mutation on codons 12 while 5 samples (38%) also had a point mutation on codons 13. No association was found between the presence of Kristen Rat Sarcoma viral oncogene mutation and gender or age or sidedness of the cancer. Kristen Rat Sarcoma viral oncogene was commonly present in colorectal cancer specimens. Further efforts towards establishment of diagnostic test, generation of new database, development and scale up of laboratory services are needed throughout the nation.

Dual-energy spectral CT characteristics in surgically resected lung adenocarcinoma: comparison between Kirsten rat sarcoma viral oncogene mutations and epidermal growth factor receptor mutations

BackgroundKirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) are the two most frequent and well-known oncogene of lung adenocarcinoma. The purpose of this study is to compare the characteristics measured with dual-energy spectral computed tomography (DESCT) in lung adenocarcinoma patients who have KRAS and EGFR gene mutations.MethodsPatients with surgically resected lung adenocarcinoma (n = 72) were enrolled, including 12 patients with KRAS mutations and 60 patients with EGFR mutations. DESCT quantitative parameters, including the CT number at 70 keV, the slopes of the spectral attenuation curves (slope λ HU), normalized iodine concentration (NIC), normalized water concentration (NWC), and effective atomic number (effective Z), were analyzed. A multiple logistic regression model was applied to discriminate clinical and DESCT characteristics between the types of mutations.ResultsThe KRAS mutation was more common in people who smoked than the EGFR mutation. Nodule type differed significantly between the KRAS and EGFR groups (P = 0.035), and all KRAS mutation adenocarcinomas were solid nodules. Most DESCT quantitative parameters differed significantly between solid nodules and subsolid nodules. CT number at 70 keV, slope λ HU, NIC, and effective Z differed significantly between the KRAS and EGFR groups (P = 0.006, 0.017, 0.013 and 0.010) with solid lung adenocarcinoma. Multivariate logistic analysis of DESCT and clinical features indicated that besides smoking history, the CT value at 70 keV (OR = 0.938, P = 0.009) was significant independent factor that could be used to differentiate KRAS and EGFR mutations in solid lung adenocarcinoma.ConclusionsDESCT would be a potential tool to differentiate lung adenocarcinoma patients with a KRAS mutation from those with an EGFR mutation.

Tailoring ablation strategies for colorectal liver metastases based upon rat sarcoma viral oncogene mutation status

Rat sarcoma viral oncogene (RAS) is one of the most well-known tumor genes implicated in the oncological and surgical management of patients with colorectal liver metastases (CLM). More recently, RAS mutational status has also emerged as a relevant factor affecting the oncological outcomes of CLM treated with ablation procedures, a well-established local therapy modality routinely utilized in the oligometastatic disease (OMD) setting. Available evidence suggests that RAS mutation is a prognosticator of shorter local tumor progression free survival (LTPFS) following liver ablation, and that mutant RAS patients with CLM treated with ablation should have wider minimal ablation margins. In this review, we aim to discuss the current literature on the influence of RAS mutational status on ablation outcomes, as well to provide a perspective on the future research on the impact of tumor molecular biology on liver ablation procedures and the potential synergies between local and systemic therapies.

The study of the relationship between clinical stage, or prognostic and kirsten rat sarcoma viral oncogene mutations of patients with pancreatic cancer detected by a nano probe

Objective To establish a method of detection kirsten rat sarcoma viral oncogene mutations in plasma by a nano capture probe system, and to explore the relationship between clinical pathology stage, or prognostic and K-ras single nucleotide polymorphism mutations in patients with pancreatic cancer. Methods The plasma samples of 72 patients with pancreatic cancer were collected from June 2013 to September 2015. The diagnosis of all patients were explicit. The DNA were extracted from all plasma samples and were detected for the codon 12 and 13 mutation of K-ras gene by nano capture probe. The relationship between clinical pathology factors, or prognostic and K-ras point mutations in pancreatic cancer was analyzed via clinical data. Results The plasma DNA concentration of 72 patients with pancreatic cancer was 20-200 ng/μl, 33 patients were detected for K-ras gene mutation, the cycle threshold (Ct) value was 21.71-35.61, including 30 patients for codon 12 mutation and 3 patients for codon 13 mutation, the K-ras mutation rate was 45.8% (33/72). 10 of 37 patients with early pancreatic cancer (stage Ⅰ and Ⅱ) were detected for K-ras gene mutation, the mutation rate was 27.0% (10/37), but 23 of 35 patients with advanced pancreatic cancer (stage Ⅲ and Ⅳ) were detected for K-ras gene mutation, the mutation rate was 65.7% (23/35), the difference is statistically significant (χ2=10.843, P=0.001), it is suggested that K-ras mutation in plasma is ralated to tumor stage. All 72 patients with pancreatic cancer were followed up, the follow-up time was 2 months to 26 months, the average follow-up time was 9.7 months. The one-year survival rate of patients with K-ras mutation is 42.6%, and the one-year survival rate of patients with wild genotype is 73.4%, the difference is statistically significant (χ2=5.335, P=0.017)). Conclusion The nano capture probe system could certainly detect K-ras mutation in rare plasma DNA. K-ras mutation in plasma is related to TMN stage and prognosis of pancreatic cancer, and K-ras mutation in plasma DNA is a predictive biomarker for a poor prognosis of pancreatic cancer patients. Key words: Pancreatic cancer; Prognosis; Mutation; Magnetic nanoparticles

The telomerase inhibitor can inhibit the malignancy of lung cancer cells with kirsten rat sarcoma viral oncogene mutation

Objective To explore the effects of telomerase inhibitor BIBR1532 on lung cancer cells with kirsten rat sarcoma viral oncogene (KRAS) mutation. Methods Human lung cancer cells (CALU3/H1299) stably transfected with lentiviral vector-mediated KRAS-mutant (the encoded amino acid from glycine mutated to aspartic acid, G12D) expression were established and the telomerase activity and the expression levels of G12D were respectively detected by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting. The proliferative activity, chemotherapy sensitivity and metastatic capability of cells were examined by methyl thiazol tetrazolium (MTT) and Scratch test. Results The telomerase activity level in KRAS-mutant lung cancer cells with telomerase inhibitors was more significantly decreased compared to KRAS wild type (KRAS-WT) lung cancer cells(the inhibition rates were about 50%). Relative to KRAS-WT cells, the KRAS-mutant cells with BIBR1532 grew and migrated more slowly, moreover, the inhibition ratio was improved more greatly (cisplatin and taxol respectively increased 10%-15% and 5%-12%). Conclusion The telomerase inhibitors could inhibit proliferative ability and metastatic capability, and increase chemotherapy sensitivity of KRAS-mutant and KRAS-WT lung cancer cells, but the variation of KRAS-mutant lung cancer cells was greater. Key words: Lung cancer; Kirsten rat sarcoma viral oncogene mutation; Telomerase inhibitors

Association Between Computed Tomographic Features and Kirsten Rat Sarcoma Viral Oncogene Mutations in Patients With Stage I Lung Adenocarcinoma and Their Prognostic Value

BackgroundWe investigated the association between computed tomographic (CT) features and Kirsten rat sarcoma viral oncogene (KRAS) mutations in patients with stage I lung adenocarcinoma and their prognostic value. Patients and MethodsA total of 79 patients with pathologic stage I lung adenocarcinoma, available KRAS mutational status, preoperative CT images available, and survival data were included in the present study. Seven CT features, including spiculation, concavity, ground-glass opacity, bubble-like lucency, air bronchogram, pleural retraction, and pleural attachment, were evaluated. The association among the clinical characteristics, CT features, and mutational status was analyzed using Student's t test, the χ2 test or Fisher's exact test, and logistic regression. The association among CT features, mutational status, and overall survival was analyzed using Kaplan-Meier survival curves with the log-rank test and Cox proportional hazard regression. ResultsThe prevalence of KRAS mutations was 41.77%. Spiculation was significantly associated with the presence of KRAS mutations (odds ratio, 2.99; 95% confidence interval [CI], 1.16-7.68). Although KRAS mutational status was not significantly associated with overall survival, the presence of pleural attachment was associated with an increased risk of death (hazard ratio, 2.46; 95% CI, 1.09-5.53). When analyzing KRAS mutational status and pleural attachment combined, patients with wild-type KRAS and no pleural attachment had significantly better survival than did those with wild-type KRAS and pleural attachment (P = .014). ConclusionThese data suggest that spiculation is associated with KRAS mutations and pleural attachment is associated with overall survival in patients with stage I lung adenocarcinoma. Combining the analysis of KRAS mutational status and CT features could better predict survival.

Pancreatic ductal adenocarcinoma with autoimmune pancreatitis-like histologic and immunohistochemical features

Autoimmune pancreatitis (AIP) often manifests as a mass lesion causing obstructive jaundice, clinically mimicking pancreatic carcinoma. A diagnosis of AIP may obviate the need for surgical resection, as most patients respond to steroid treatment. However, it is not clear whether these 2 conditions can coexist. In this study, 105 specimens resected for pancreatic ductal adenocarcinoma (PDAC) that also have changes of chronic pancreatitis were examined for features considered to be characteristic of AIP. Of 105 cases of PDAC with changes of chronic pancreatitis, 10 (9.5%) exhibited histologic features of AIP, including exuberant fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, or granulocytic epithelial lesions. Of these 10 cases, 7 had more than 20 immunoglobulin G4+ plasma cells per high-power field. Of these 7 cases, 5 were analyzed for Kirsten rat sarcoma viral oncogene mutation and SMAD4 expression. Three cases showed K-ras mutation and/or loss of SMAD4 expression in benign AIP-like areas. These findings suggest 2 possibilities: first, AIP-like lesions may occur in a small but significant portion of PDAC cases; second, some PDACs may arise in a background of AIP. Therefore, caution is necessary when making a diagnosis of AIP by needle biopsy of a mass lesion, and patients with a tentative AIP diagnosis should be closely followed up clinically.