摘要
背景与目的:肿瘤组织和细胞中的miR-21先后被证实与肿瘤对化疗药物的敏感性有关,高表达miR-21提示肿瘤对多种化疗药物不敏感。外周血蕴含丰富的肿瘤信息,为个体化药物治疗提供了新的检测来源。本研究初步探讨胃癌组织和血浆循环miR21表达水平与胃癌铂类药物和伊立替康敏感性之间的关系。方法:系统收集35例经病理确诊的新鲜人胃癌标本,采用三维微组织块培养法行两种药物的体外敏感试验;实时荧光定量PCR检测血浆和对应胃癌石蜡组织中miR-21表达水平。结果:血浆miR21与对应肿瘤组织miR-21呈正相关(rho=O.736,P〈0.001)。血浆miR-21水平与性别、年龄、病理类型、分化程度、淋巴结转移、TNM分期、肿瘤部位无统计学相关性,但是II期和III期的miR-21水平较I期有偏高的趋势。铂类药物敏感组与耐药组肿瘤组织miR-21相对表达量分别为1.32(95%CI:0.73-1.90)和4.06(95%CI:1.71~6.41),差异无统计学意义(P=0.004);铂类药物敏感组与耐药组血浆miR-21相对表达量分别为5.25(95%CI:0.14~10.64)和5.82(95%,差异无统计学意义a:2.27~9.37),差异无统计学意义(P-0.19)。伊立替康敏感组与耐药组肿瘤组织miR-21相对表达量分别为1.09(95%CI:0.65~1.54)和4.94(95%CI:2.44~7.44),差异无统计学意义(P〈0.001);伊立替康敏感组与耐药组血浆miR-21JfN对表达量分别为1.86(95%CI:1.08~2.64)和12.42(95%CI:3.14~21.70)差异无统计学意义(P=0.001)。结论:血浆循环miR-21与对应肿瘤组织miR-2l水平呈显著正相关,在一定程度上能反映肿瘤组织miR-21的水平。血浆miR-21水平与新鲜胃癌组织对伊立替康的敏感性呈负相关,肿瘤组织miR-2l水平与新鲜胃癌组织对伊立替康和铂类药物的敏感性呈负相关。
Background and purpose: Mir-21 has been demonstrated high expressed in many kinds of tumor tissues and cell lines. High expressed miR-21 leads to chemoresistance. Circulating miRNA is a novel biomarker for chemosensitivity prediction. The aim of our study was to investigate the role of plasma and tumor miR-21 levels as predictive biomarkers for irinotecan in gastric cancer. Methods: The histoculture drug response assay (HDRA) was used to determine irinotecan and cisplatin sensitivity on 35 freshly removed gastric tumor specimens, miR-21 expressions in tumor and plasma were determined by quantitative reverse transcription polymerase chain reaction. Results: Plasma miR-21 was closely correlated with corresponding miR-21 mRNA level in tumor tissues (rho=0.736, P〈0.001) and was not correlated with sex, age, pathology type, differentiation, lymph node metastasis, TNM stage or tumor location. Patients with stage Ⅱ- Ⅲ had higher miR-21 levels. The tumor miR-21 expressions in cisplatin- sensitive group and resistant group were 1.32 (95%CI: 0.73-1.90) and 4.06 (95%CI: 1.71-6.41)(P=0.004), respectively. The plasma miR-21 expressions in cisplatin-sensitive group and resistant group were 5.25 (95% CI: O. 14-10.64) and5,82 (95%CI: 2.27-9.37)(P=0.19). The tumor miR-21 expressions in irinotecan-sensitive group and resistant group were 1.09 (95%CI: 0.65-l.54) and 4.94 (95%CI: 2.44-7.44)(P〈0.001), respectively. The plasma miR-21 expressions in irinotecan-sensitive group and resistant group were 1.86 (95%CI: 1.08-2.64) and 12.42 (95%CI: 3.14-21.70)(P=0.001). Conclusion: A significant correlation was observed between plasma and tumor miR-21 level. The low plasma miR- 2l level could benefit from treatment with irinotecan. And low tumor miR-21 expression correlated with increased irinotecan and cisplatin response rate.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2013年第9期744-750,共7页
China Oncology