胃癌组织和循环miR-21与胃癌伊立替康敏感性关系的初步研究

Circulating and tumor miR-21 could predict irinotecan sensitivity in gastric cancer

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.