肿瘤浸润性反映了许多生物学变化，包括肿瘤发生、发展和转移。为了解编码转录调控因子（TR）在肿瘤浸润性中的作用，我们进行了一个系统的基于网络的全癌种分类评估，寻找癌症浸润性的主调控因子。我们根据一个已建立的可靠的24基因签名，通过共识聚类将癌症基因组图谱(ATCG)中的患者分为浸润性高(INV-H)和低(INV-L)群组，并确定浸润性与32种不同癌种的整体生存期(OS)的预后关联。我们设计了一个基于网络的方法来识别特定于INV-H和INV-L表型的主调控因子(MR)。我们在从基因组数据分析中预测临床结果(PRECOG)存储库中的一系列额外数据集上验证了在TCGA中与INV-H表型和较差OS一致相关的MRs。根据24基因签名，我们为每个患者样本定义了浸润性评分，并将患者分为INV-H和INV-L群组。我们观察到，几乎所有癌症中浸润性与较差的生存结果相关，并在32种癌症中有10种与OS有显著关联。我们的基于网络的框架在这十种癌症中识别了普遍的与浸润性相关的MRs，包括COL1A1，它也是24基因签名的一部分，因此可作为阳性对照。对与INV-H表型特异性的MRs的后续通路分析导致了多个富集的通路的发现，包括上皮向间质过渡、TGF-β信号通路、Toll样受体、细胞因子和炎症反应调节，以及T细胞极化期间特选择性表达的趋化因子受体。大多数这些通路都与炎症免疫应答和转移的可行性有关。我们的全癌研究提供了肿瘤浸润性的全面主调控因子分析，并可为跨多个癌症的患者通过靶向识别的MR和下游富集通路提供更精确的治疗策略。© 2023 年。BioMed Central有限公司，Springer Nature的组成部分。

Tumor invasiveness reflects numerous biological changes, including tumorigenesis, progression, and metastasis. To decipher the role of transcriptional regulators (TR) involved in tumor invasiveness, we performed a systematic network-based pan-cancer assessment of master regulators of cancer invasiveness.We stratified patients in The Cancer Genome Atlas (TCGA) into invasiveness high (INV-H) and low (INV-L) groups using consensus clustering based on an established robust 24-gene signature to determine the prognostic association of invasiveness with overall survival (OS) across 32 different cancers. We devise a network-based protocol to identify TRs as master regulators (MRs) unique to INV-H and INV-L phenotypes. We validated the activity of MRs coherently associated with INV-H phenotype and worse OS across cancers in TCGA on a series of additional datasets in the Prediction of Clinical Outcomes from the Genomic Profiles (PRECOG) repository.Based on the 24-gene signature, we defined the invasiveness score for each patient sample and stratified patients into INV-H and INV-L clusters. We observed that invasiveness was associated with worse survival outcomes in almost all cancers and had a significant association with OS in ten out of 32 cancers. Our network-based framework identified common invasiveness-associated MRs specific to INV-H and INV-L groups across the ten prognostic cancers, including COL1A1, which is also part of the 24-gene signature, thus acting as a positive control. Downstream pathway analysis of MRs specific to INV-H phenotype resulted in the identification of several enriched pathways, including Epithelial into Mesenchymal Transition, TGF-β signaling pathway, regulation of Toll-like receptors, cytokines, and inflammatory response, and selective expression of chemokine receptors during T-cell polarization. Most of these pathways have connotations of inflammatory immune response and feasibility for metastasis.Our pan-cancer study provides a comprehensive master regulator analysis of tumor invasiveness and can suggest more precise therapeutic strategies by targeting the identified MRs and downstream enriched pathways for patients across multiple cancers.© 2023. BioMed Central Ltd., part of Springer Nature.