Bi Guoshu, Liang Jiaqi, Zheng Yuansheng, Li Runmei, Zhao Mengnan, Huang Yiwei, Zhan Cheng, Xu Songtao, Fan Hong
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, China.
Department of Biostatistics, Public Health, Fudan University, Shanghai, 200000, China.
J Transl Med. 2021 Mar 25;19(1):124. doi: 10.1186/s12967-021-02773-x.
Tumor invasiveness reflects many biological changes associated with tumorigenesis, progression, metastasis, and drug resistance. Therefore, we performed a systematic assessment of invasiveness-related molecular features across multiple human cancers.
Multi-omics data, including gene expression, miRNA, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus, PRECOG, and our institution were enrolled in this study.
Based on a robust gene signature, we established an invasiveness score and found that the score was significantly associated with worse prognosis in almost all cancers. Then, we identified common invasiveness-associated dysregulated molecular features between high- and low-invasiveness score group across multiple cancers, as well as investigated their mutual interfering relationships thus determining whether the dysregulation of invasiveness-related genes was caused by abnormal promoter methylation or miRNA expression. We also analyzed the correlations between the drug sensitivity data from cancer cell lines and the expression level of 685 invasiveness-related genes differentially expressed in at least ten cancer types. An integrated analysis of the correlations among invasiveness-related genetic features and drug response were conducted in esophageal carcinoma patients to outline the complicated regulatory mechanism of tumor invasiveness status in multiple dimensions. Moreover, functional enrichment suggests the invasiveness score might serve as a predictive biomarker for cancer patients receiving immunotherapy.
Our pan-cancer study provides a comprehensive atlas of tumor invasiveness and may guide more precise therapeutic strategies for tumor patients.
肿瘤侵袭性反映了许多与肿瘤发生、进展、转移和耐药性相关的生物学变化。因此，我们对多种人类癌症中与侵袭性相关的分子特征进行了系统评估。
本研究纳入了来自癌症基因组图谱、基因表达综合数据库、PRECOG以及我们机构的约10000名患者的多组学数据，包括基因表达、miRNA、DNA甲基化和体细胞突变，涉及30种癌症类型。
基于一个强大的基因特征，我们建立了一个侵袭性评分，并发现该评分在几乎所有癌症中都与较差的预后显著相关。然后，我们在多种癌症的高侵袭性评分组和低侵袭性评分组之间确定了常见的与侵袭性相关的失调分子特征，并研究了它们之间的相互干扰关系，从而确定侵袭性相关基因的失调是否由启动子甲基化异常或miRNA表达异常引起。我们还分析了癌细胞系的药物敏感性数据与至少在十种癌症类型中差异表达的685个侵袭性相关基因的表达水平之间的相关性。对食管癌患者侵袭性相关遗传特征与药物反应之间的相关性进行了综合分析，以从多个维度勾勒肿瘤侵袭性状态的复杂调控机制。此外，功能富集分析表明侵袭性评分可能作为接受免疫治疗的癌症患者的预测生物标志物。
我们的泛癌研究提供了一个全面的肿瘤侵袭性图谱，并可能为肿瘤患者指导更精确的治疗策略。
