微卫星稳定的胃癌可分为2种分子亚型,具有不同的免疫疗法反应和基于基因测序和计算病理学的预后
Zhiyi Ye1, Xiaoyang Wu1, Zheng Wei1
1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, China; Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, China.
概括
这项研究开发了一种使用免疫相关基因和深度学习来分类微卫星稳定的胃癌 (GC) 的新方法. 这种方法可以改善预后预测,并指导个性化治疗策略,以获得更好的患者结果.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 大多数胃癌 (GC) 患者具有微卫星稳定性,但缺乏用于预后和治疗的特定亚型.
- 目前微观卫星稳定的GC的分类方法对于临床决策是不够的.
研究的目的:
- 开发和验证一种新的免疫相关基因 (IRG) 签名,用于微观卫星稳定的GC亚型.
- 创建深度学习模型,用于预测GC瘤块,并从病理幻灯片中识别微卫星稳定的GC亚型.
- 评估已识别的微卫星稳定的GC亚型的预后价值和治疗影响.
主要方法:
- 利用RNA测序基因表达和来自TCGA和GEO数据库的微观卫星稳定的GC患者的临床数据.
- 使用机器学习建立5-IRG签名,将患者分为高风险 (微卫星稳定-HR) 和低风险 (微卫星稳定-LR) 组.
- 开发基于视觉转换器 (ViT) 的深度学习模型,用于使用数字病理图像进行瘤细分和亚型分类.
主要成果:
- 一个5-IRG签名有效地分层了微卫星稳定的GC患者,显示出一致的预后表现 (AUC从0.60到0.70不等).
- 微卫星稳定HR亚型显示免疫功能障碍和排斥增加,表明潜在的免疫逃脱.
- 深度学习模型实现了高精度 (瘤识别AUC为0.97和亚型识别为0.94),在外部队列中验证亚型分类.
结论:
- 开发的IRG签名和深度学习模型为微卫星稳定的GC亚型提供了强大的方法.
- 这些亚型表现出不同的免疫特征和不同的药物敏感性,为精准医学铺平了道路.
- 这项研究有可能提高预后准确性,并为微观卫星稳定的GC患者提供量身定制的治疗策略,最终改善结果.
相关概念视频
02:18Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
02:40Cancer Stem Cells and Tumor Maintenance
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...