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Cold Spring Harb Mol Case Stud:生物信息学家利用RNA测序指导胃癌的个性化药物处方方法

2020-06-26 转化医学网 转化医学网

胃癌是源自胃黏膜上皮的恶性肿瘤,在我国各种恶性肿瘤中发病率居首位。由于饮食结构改变、工作压力增大等原因,使得胃癌的发病呈现年轻化趋势。

免疫治疗是目前胃癌的最新治疗手段,然而,患者对治疗的反应往往是不可预测的,因此需要针对具体情况制定个性化疗法和药物处方。近日,莫斯科物理技术学院(MIPT)的研究人员首次开发了一种基于肿瘤细胞RNA测序的个性化胃癌治疗技术,给胃癌的治疗带来了新的思路。

这项研究由莫斯科物理技术学院转化基因组生物信息学实验室高级研究员Maxim Sorokin领导,并在俄罗斯科学基金会的支持下发表在《冷泉港分子案例研究》上。题目为“RNA sequencing profiles and diagnostic signatures linked with response to ramucirumab in gastric cancer”

胃癌的相关死亡率在所有癌症中排名第五。由于早期诊断的比例很低,大多数患者被诊断出来时就已经为晚期。对于HER2阳性病例,一线治疗标准包括氟嘧啶和铂类化合物配合曲妥珠单抗。对于复发性胃癌,有几种替代选择,包括雷米库单抗,一种单克隆治疗性抗体,可通过与VEGFR2结合,单独或与其他癌症药物配合来抑制VEGF介导的肿瘤血管生成。然而,雷米库单抗或其混合体的总反应率占患者总数的30%–80%,这表明胃癌的治疗需要个性化药物处方以提高治疗效果。

MIPT的生物信息学家研究了15位胃癌晚期患者的原始肿瘤RNA测序情况,以及对雷米库单抗或其混合体的临床反应。结果显示,有三个基因在肿瘤中显示出不同程度的表达:CHRM3,LRFN1和TEX15。其中,CHRM3的表达在反应中上调。研究人员使用生物信息平台Oncobox,模拟了雷米库单抗的效率,并将输出模型结果与实际的肿瘤反应数据进行了比较。结果发现,预测的临床结果与实际的临床结果一致(AUC≥0.7)。这些结果表明,RNA测序可用于筛选雷米库单抗治疗胃癌的个性化处方,并揭示了雷米库单抗耐药性的潜在分子机制。

用治疗性抗体治疗胃部的复发性肿瘤,它们阻断负责接收促进生长信号的细胞表面受体。没有它们,细胞分裂就会停止,肿瘤的大小不会增加。在癌症治疗中,阻止血管的生长特别重要,因为血管为肿瘤提供了营养和氧气。雷米库单抗是一种治疗性抗体,用于破坏肿瘤组织中血管的生长。但该药物的功效因人而异。

此前,MIPT的生物信息学家以及医学研究中心和行业内专家建议,可以将患者有关癌症基因表达水平的数据,用于评估不同情况下的雷米库单抗的疗效。

该研究的第一作者,MIPT转化基因组生物信息学实验室高级研究员和Oncobox生物信息学系主任Maxim Sorokin说:“这次研究实际上是第一个成功为胃癌患者开出[雷米库]处方的病例,这不是随机的,而是通过我们基于RNA测序追踪的分子标记分析得出的信息。”

结合信息技术,现代分子生物学方法使研究人员能够收集细胞中每个基因表达的定性数据。通过分析这些数据,可以找到诊断肿瘤疾病和预测其治疗效果的关键。

原始出处:

Maxim Sorokin, et al. RNA sequencing profiles and diagnostic signatures linked with response to ramucirumab in gastric cancer. Cold Spring Harb Mol Case Stud 6: a004945. doi: 10.1101/mcs.a004945.

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    2021-01-23 charl1234567
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    2021-01-14 zhouqu_8
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    2020-06-28 yaanren

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