BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are em...BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers,but their potential for screening colorectal neoplasms remains ambiguous.AIM To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.METHODS The study was divided into three phases:(1)Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods;(2)an independent set of serum samples from 60 CRC patients,60 AA patients and 30 healthy controls(HCs)was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs,and their diagnostic power was detected by receiver operating characteristic(ROC)analysis;and(3)the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.RESULTS Based on bioinformatics analysis,miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study.Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs.The diagnostic power of miR-672-5p yielded an area under the curve(AUC)value of 0.90,and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs.A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA.Additionally,the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines,suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived.Furthermore,in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.CONCLUSION Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.展开更多
背景与目的:CPT-11联合5-FU/CF(FOLFIRI)化疗方案是治疗晚期结直肠癌的有效方案。但是,该方案作为一线方案治疗中国晚期结直肠癌患者的资料缺乏,其疗效和安全性仍需进一步确定。本文旨在探讨FOLFIRI方案作为一线治疗方案对中国晚期结直...背景与目的:CPT-11联合5-FU/CF(FOLFIRI)化疗方案是治疗晚期结直肠癌的有效方案。但是,该方案作为一线方案治疗中国晚期结直肠癌患者的资料缺乏,其疗效和安全性仍需进一步确定。本文旨在探讨FOLFIRI方案作为一线治疗方案对中国晚期结直肠癌患者的疗效和安全性。方法:自2002年1月至2005年9月期间,共54例晚期结直肠癌患者采用FOLFIRI方案作为一线方案进行治疗,回顾性分析其治疗有效率(response rate,RR)、疾病进展时间(time to progression,TTP)、总生存时间(overall survival,OS)和不良反应。结果:54例患者中52例可评价疗效。其中RR为42.6%,TTP为6个月,OS为15.2个月。最常见的不良反应为中性粒细胞减少(38.9%)、腹泻(37.1%)和恶心呕吐(50.0%),Ⅲ/Ⅳ级的发生率分别为5.6%、9.3%和9.3%,总体耐受性好。结论:FOLFIRI方案治疗中国晚期结直肠癌患者疗效肯定,作为一线化疗方案有较高的有效性,不良反应可以耐受。展开更多
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers,but their potential for screening colorectal neoplasms remains ambiguous.AIM To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.METHODS The study was divided into three phases:(1)Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods;(2)an independent set of serum samples from 60 CRC patients,60 AA patients and 30 healthy controls(HCs)was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs,and their diagnostic power was detected by receiver operating characteristic(ROC)analysis;and(3)the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.RESULTS Based on bioinformatics analysis,miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study.Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs.The diagnostic power of miR-672-5p yielded an area under the curve(AUC)value of 0.90,and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs.A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA.Additionally,the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines,suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived.Furthermore,in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.CONCLUSION Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.
文摘背景与目的:CPT-11联合5-FU/CF(FOLFIRI)化疗方案是治疗晚期结直肠癌的有效方案。但是,该方案作为一线方案治疗中国晚期结直肠癌患者的资料缺乏,其疗效和安全性仍需进一步确定。本文旨在探讨FOLFIRI方案作为一线治疗方案对中国晚期结直肠癌患者的疗效和安全性。方法:自2002年1月至2005年9月期间,共54例晚期结直肠癌患者采用FOLFIRI方案作为一线方案进行治疗,回顾性分析其治疗有效率(response rate,RR)、疾病进展时间(time to progression,TTP)、总生存时间(overall survival,OS)和不良反应。结果:54例患者中52例可评价疗效。其中RR为42.6%,TTP为6个月,OS为15.2个月。最常见的不良反应为中性粒细胞减少(38.9%)、腹泻(37.1%)和恶心呕吐(50.0%),Ⅲ/Ⅳ级的发生率分别为5.6%、9.3%和9.3%,总体耐受性好。结论:FOLFIRI方案治疗中国晚期结直肠癌患者疗效肯定,作为一线化疗方案有较高的有效性,不良反应可以耐受。
