The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC pat...The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China.The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively.KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction(q-PCR)in 410 CRC patients,with mutation frequencies of KRAS,NRAS and BRAF of 47.56%,2.93%and 4.15%,respectively.The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed.The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes.The BRAF gene mutation was also associated with cancer thrombosis in blood vessels.Cox regression analysis showed that there was no statistically significant difference in the overall survival(OS)between patients with KRAS,NRAS mutants and wild-type CRC patients,while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients.It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.展开更多
Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leu...Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leukemia and is generally associated with a poor prognosis.2 CMML predominantly affects older adults,and treatment often involves demethylation therapy tailored to the patient's age and overall health.3 However,the complete remission rate for patients with CMML undergoing demethylation therapy is<20%and is frequently accompanied with severe side effects.1 Here,we discuss the case of an 84-year-old male diagnosed with CMML 6 years earlier,who experienced significant bone marrow suppression following demethylation therapy.By integrating multiomics data with bioinformatics,we developed and applied a novel approach of trimetinib monotherapy.This treatment resulted in notable improvements in hematopoietic function and overall quality of life,offering a promising strategy for managing CMML.展开更多
BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qua...BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.展开更多
基金the National Natural Science Foundation of China(No.81472707)Chinese South Western Oncology Group(CSWOG-CCET005).
文摘The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China.The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively.KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction(q-PCR)in 410 CRC patients,with mutation frequencies of KRAS,NRAS and BRAF of 47.56%,2.93%and 4.15%,respectively.The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed.The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes.The BRAF gene mutation was also associated with cancer thrombosis in blood vessels.Cox regression analysis showed that there was no statistically significant difference in the overall survival(OS)between patients with KRAS,NRAS mutants and wild-type CRC patients,while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients.It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.
基金supported by the Multi-Center Clinical Research Project of the National Clinical Research Center for Geriatric Diseases(No.NCRCG-PLAGH-20230010)the Key Military Health Project(No.23BJZ25).
文摘Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leukemia and is generally associated with a poor prognosis.2 CMML predominantly affects older adults,and treatment often involves demethylation therapy tailored to the patient's age and overall health.3 However,the complete remission rate for patients with CMML undergoing demethylation therapy is<20%and is frequently accompanied with severe side effects.1 Here,we discuss the case of an 84-year-old male diagnosed with CMML 6 years earlier,who experienced significant bone marrow suppression following demethylation therapy.By integrating multiomics data with bioinformatics,we developed and applied a novel approach of trimetinib monotherapy.This treatment resulted in notable improvements in hematopoietic function and overall quality of life,offering a promising strategy for managing CMML.
文摘BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.
