6109 POSTER Difference in Overall Survival in Colorectal Cancer Patients With the KRas P.G13D and Other KRas Mutations After the Failure of 5-fluorouracil, Oxaliplatin, and Irinotecan

2011 ◽  
Vol 47 ◽  
pp. S424-S425
Author(s):  
K. Suvama ◽  
T. Yoshino ◽  
Y. Kawamoto ◽  
H. Bando ◽  
T. Doi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Kras Mutations ◽  
Colorectal Cancer Patients

scholarly journals Clinical characteristics and prognostic value of the KRAS mutation in Chinese colorectal cancer patients

2021 ◽  
pp. 172460082110171
Author(s):  
Ye Yuan ◽  
Yingting Liu ◽  
Ye Wu ◽  
Junling Zhang ◽  
Chunti Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
High Frequency ◽  
Kras Mutation ◽  
Chinese Patients ◽  
Wild Type ◽  
Kras Mutations ◽  
Exon 2 ◽  
Colorectal Cancer Patients

Background: The KRAS mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of KRAS, other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of KRAS in Chinese colorectal cancer patients and to investigate their impact on prognosis. Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of KRAS mutations. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect KRAS mutations. Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutations. The most frequent of these mutations were G12D (32.19%), G12V (17.96%), and G13D (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%), and G14D (3.92%) were high-frequency. The KRAS mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; P=0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; P=0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; P=0.026), and KRAS mutation (HR 1.897; 95% Cl 0.19, 0.90; P=0.001) remained independent predictors of shorter overall survival. Among the common KRAS mutations, G12D was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; P < 0.0001) compared with KRAS wild-type patients. Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the KRAS G12D mutation subtype. We found that the KRAS G12D mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by G12D-specific related inhibitors.

scholarly journals KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan: Molecular spectrum, frequency and distribution pattern

2019 ◽  
Author(s):  
Muhammad Awidi ◽  
Nidaa Ababneh ◽  
Maha Shomaf ◽  
Feras Al Fararjeh ◽  
Laila Owaidi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Distribution Pattern ◽  
Cancer Patients ◽  
Molecular Spectrum ◽  
Kras Mutations ◽  
Exon 2 ◽  
Ras Mutations ◽  
Colorectal Cancer Patients ◽  
Kras Exon

Abstract Background A constitutively active RAS protein in the absence of stimulation of the epidermal growth factor receptor (EGFR) is the result of mutations in KRAS and NRAS genes. Mutations in the KRAS exon 2 and outside exon 2 have been found to predict the resistance to anti-EGFR monoclonal therapy. A substantial proportion of metastatic colorectal cancer cases (mCRC) exhibit RAS mutations outside KRAS exon 2, particularly in KRAS exon 3 and 4 and NRAS exons 2, 3. No data about RAS mutations outside KRAS exon 2 are available for Jordanian patients with mCRC. We aim to study the molecular spectrum, frequency, and distribution pattern of KRAS and NRAS mutations in Jordanian patients with mCRC. Methods A cohort of 190 Jordanian metastatic colorectal cancer patients were enrolled in the trial. We detected mutations in exon 2 of the KRAS and NRAS gene as well as mutations outside of exon 2 using the StripAssay technique. The KRAS StripAssay covered 29 mutations and 22 NRAS mutations. Results Mutations were observed in 92 (48.42%) cases, and KRAS exon 2 accounted for 76 cases (83.69%). KRAS G12D was the most common mutation, occurring in 18 cases, followed by KRAS G12A in 16 cases, and G12T in 13 cases. Mutations outside of KRAS exon 2 represented 16.3% of the mutated cases. Among those, 6 cases (6.48%) carried mutations in NRAS exon 2, 3 and 10 cases (10.87%) in KRAS exon 3 and 4. Conclusion The frequency of NRAS and KRAS mutations outside of exon 2 appears to be higher in Jordanian patients in comparison with patients from western countries. KRAS mutations outside of exon 2 should be tested routinely to identify patients who should not be treated with anti-EGFR antibodies.

scholarly journals IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Renato Morato ZANATTO ◽  
Gianni SANTOS ◽  
Júnea Caris OLIVEIRA ◽  
Eduardo Marcucci PRACUCHO ◽  
Adauto José Ferreira NUNES ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Direct Sequencing ◽  
Colorectal Carcinogenesis ◽  
Kras Mutations ◽  
Primary Tumor Site ◽  
Exon 2 ◽  
Metastatic Site ◽  
Colorectal Cancer Patients

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

scholarly journals PIK3CAandTP53mutations predict overall survival of stage II/III colorectal cancer patients

2018 ◽  
Vol 24 (5) ◽  
pp. 631-640 ◽  
Author(s):  
A-Jian Li ◽  
Hua-Guang Li ◽  
Er-Jiang Tang ◽  
Wei Wu ◽  
Ying Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Stage Ii ◽  
Colorectal Cancer Patients

scholarly journals Higher titer hepatitis B core antibody predicts a higher risk of liver metastases and worse survival in patients with colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziyao Li ◽  
Shaofei Li ◽  
Hangbo Tao ◽  
Yixiang Zhan ◽  
Kemin Ni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Hepatitis B ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Hepatic Metastasis ◽  
High Titer ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Colorectal Cancer Patients

Abstract Background There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients. Methods Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed. Results Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718–7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789–11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054–13.369; P = .041) in the anti-HBc positive cases. Conclusions Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.

Predicting biomarkers of hepatic metastasis in Chinese colorectal cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
Honghua Peng ◽  
Tianhao Mu ◽  
Yaping Sheng ◽  
Yingmei Li ◽  
Peiguo Cao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hepatic Metastasis ◽  
Primary Tumor ◽  
Potential Candidate ◽  
Poor Overall Survival ◽  
Primary Tumors ◽  
Distant Spread ◽  
Colorectal Cancer Patients

e15545 Background: Hepatic metastasis is the most common site of distant spread from colorectal cancer. About 15-25% patients with colorectal cancer harbors hepatic metastasis. The molecular mechanism and predicting biomarkers in colorectal cancer are still not fully understood. Methods: 57 Chinese colorectal cancer patients were enrolled in a cohort study. Samples of primary tumor were collected in these patients and underwent whole exome sequencing. Mutation profiles of primary tumors between the patients with metastasis and those without metastasis were analyzed and compared. Results: In the cohort, 54.4% (31/57) patients presented hepatic metastasis at the time of diagnosis, while 45.6% (26/57) did not. The patients were divided into 2 groups—with hepatic metastasis and without hepatic metastasis. The mutation landscape of primary tumor indicated that the Top 3 most frequently mutated genes of both groups were the same and presented mutated TP53, APC, and KRAS. 2. Interestingly, compared with the patients without hepatic metastasis, the patients with hepatic metastasis presented a higher frequency of mutated TCF7L2 (35.5% vs 3.85%) and TRIM77 (16.1% vs 0%). Moreover, in the patients with hepatic metastasis, the patients with TRIM77 mutation in primary tumor showed a worse overall survival (p < 0.0001). Conclusions: TCF7L2 and TRIM77 may be identified as potential candidate predicting biomarkers for hepatic metastasis in colorectal patients. In addition, mutated TRIM 77 predicted a poor overall survival in hepatic metastasis from colorectal cancer.

Sign in / Sign up

Export Citation Format

Share Document