Machine Learning-based Framework Develops a Tumor Thrombus Coagulation Signature in Multicenter Cohorts for Renal Cancer

基于机器学习的框架在多中心肾癌队列中开发肿瘤血栓凝固特征

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作者:Tao Feng, Yue Wang, Wei Zhang, Tingting Cai, Xi Tian, Jiaqi Su, Zihao Zhang, Shengfeng Zheng, Shiqi Ye, Bo Dai, Ziliang Wang, Yiping Zhu, Hailiang Zhang, Kun Chang, Dingwei Ye

Background

Renal cell carcinoma (RCC) is frequently accompanied by tumor thrombus in the venous system with an extremely dismal prognosis. The current Tumor Node Metastasis (TNM) stage and Mayo clinical classification do not appropriately identify preference-sensitive treatment. Therefore, there is an urgent need to develop a better ideal model for precision medicine.

Conclusions

The TTCRRS signature can complement the traditional anatomic TNM staging system and Mayo clinical stratification and provide clinicians with more therapeutic options.

Methods

In this study, we developed a coagulation tumor thrombus signature for RCC with 10 machine-learning algorithms (101 combinations) based on a novel computational framework using multiple independent cohorts.

Results

The established tumor thrombus coagulation-related risk stratification (TTCRRS) signature comprises 10 prognostic coagulation-related genes (CRGs). This signature could predict survival outcomes in public and in-house protein cohorts and showed high performance compared to 129 published signatures. Additionally, the TTCRRS signature was significantly related to some immune landscapes, immunotherapy response, and chemotherapy. Furthermore, we also screened out hub genes, transcription factors, and small compounds based on the TTCRRS signature. Meanwhile, CYP51A1 can regulate the proliferation and migration properties of RCC. Conclusions: The TTCRRS signature can complement the traditional anatomic TNM staging system and Mayo clinical stratification and provide clinicians with more therapeutic options.

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