目的:目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证,探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法:利用生物信息学,我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p...目的:目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证,探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法:利用生物信息学,我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p Background: The role of m6A methylation genes in the differentiation of colorectal cancer is currently unclear. This study combines bioinformatics analysis and experimental validation to explore the expression patterns of these genes in colorectal cancer and their potential mechanisms. Methods: Using bioinformatics, we found that YTHDF1, YTHDF2, ALKBH5, and WTAP are significantly aberrantly expressed in colorectal cancer (p < 0.05). In a real-world cohort from Lishui, quantitative PCR (qPCR) was used to measure mRNA expression of these four genes in CRC tissues and adjacent normal tissues. Multivariable logistic regression analysis with SPSS identified YTHDF1 and WTAP mRNA expression levels as being associated with CRC differentiation. Immunohistochemistry (IHC) was performed to examine corresponding protein levels, quantified using ImageJ. Results showed that YTHDF1 protein expression negatively correlated with CRC differentiation, whereas WTAP protein expression positively correlated. Additionally, multivariable Cox regression analysis was conducted to identify potential factors influencing CRC development. Results: In Lishui, YTHDF1 protein expression was negatively associated with CRC differentiation, while WTAP protein expression was positively associated. Age and alcohol consumption were key risk factors for CRC development, while no significant associations were found with sex or smoking. GO enrichment analysis suggests that YTHDF1 and WTAP may regulate the differentiation process of colorectal cancer by participating in mechanisms such as mRNA modification, translation regulation, and RNA stability. For the poorly differentiated CRC group, time to progression rate (TTP) was 100% and overall survival rate (OS) was 0% within three years. Conclusions: In Lishui City, the YTHDF1 and WTAP genes influence the differentiation of colorectal cancer and may serve as important therapeutic targets and biomarkers for the diagnosis of patients with colorectal cancer.展开更多
Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxic...Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.展开更多
文摘目的:目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证,探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法:利用生物信息学,我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p Background: The role of m6A methylation genes in the differentiation of colorectal cancer is currently unclear. This study combines bioinformatics analysis and experimental validation to explore the expression patterns of these genes in colorectal cancer and their potential mechanisms. Methods: Using bioinformatics, we found that YTHDF1, YTHDF2, ALKBH5, and WTAP are significantly aberrantly expressed in colorectal cancer (p < 0.05). In a real-world cohort from Lishui, quantitative PCR (qPCR) was used to measure mRNA expression of these four genes in CRC tissues and adjacent normal tissues. Multivariable logistic regression analysis with SPSS identified YTHDF1 and WTAP mRNA expression levels as being associated with CRC differentiation. Immunohistochemistry (IHC) was performed to examine corresponding protein levels, quantified using ImageJ. Results showed that YTHDF1 protein expression negatively correlated with CRC differentiation, whereas WTAP protein expression positively correlated. Additionally, multivariable Cox regression analysis was conducted to identify potential factors influencing CRC development. Results: In Lishui, YTHDF1 protein expression was negatively associated with CRC differentiation, while WTAP protein expression was positively associated. Age and alcohol consumption were key risk factors for CRC development, while no significant associations were found with sex or smoking. GO enrichment analysis suggests that YTHDF1 and WTAP may regulate the differentiation process of colorectal cancer by participating in mechanisms such as mRNA modification, translation regulation, and RNA stability. For the poorly differentiated CRC group, time to progression rate (TTP) was 100% and overall survival rate (OS) was 0% within three years. Conclusions: In Lishui City, the YTHDF1 and WTAP genes influence the differentiation of colorectal cancer and may serve as important therapeutic targets and biomarkers for the diagnosis of patients with colorectal cancer.
基金Natural Science Foundation of Gansu Province(Project No.:24JRRA615)Outstanding Talent Recruitment Program and the Doctoral Start-up Fund of Gansu Provincial Central Hospital(Project No.:GMCCH2024-2-6)。
文摘Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.
