Su Guoqing, Wang Meiqin, Qian Jinghang, Wang Yang, Zhu Yu, Wang Nannan, Wang Ke, Wang Qifan, Wang Yi, Li Dongzheng, Yang Liu
Department of Colorectal Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China.
Biomedicines. 2024 Sep 30;12(10):2225. doi: 10.3390/biomedicines12102225.
The intricate interplay between the platelet-coagulation system and the progression of malignant tumors has profound therapeutic implications. However, a thorough examination of platelet and coagulation markers specific to colorectal cancer (CRC) is conspicuously absent in the current literature. Consequently, there is an urgent need for further exploration into the mechanistic underpinnings of these markers and their potential clinical applications.
By integrating RNA-seq data and clinicopathological information from patients with CRC in the cancer genome atlas, we identified genes related to the platelet-coagulation system using weighted gene co-expression networks and univariate Cox analysis. We established a prognostic risk model based on platelet- and coagulation-related genes using Lasso Cox regression analysis and validated the model in two independent CRC cohorts. We explored potential biological functional disparities between high-risk and low-risk groups through comprehensive bioinformatics analysis.
Our findings indicate that colorectal cancer patients classified as high-risk generally exhibit poorer prognoses. Moreover, the model's risk scores were associated with the differential composition of the immune tumor microenvironment, suggesting its applicability to infer immunotherapy responsiveness. Cellular functional experiments and animal experiments indicated that CYP19A1 expression in CRC influences malignant phenotype and platelet activation.
In summary, we present a novel platelet- and coagulation-related risk model for prognostic assessment of patients with CRC and confirm the important role of CYP19A1 in promoting malignant progression of CRC.
血小板-凝血系统与恶性肿瘤进展之间复杂的相互作用具有深远的治疗意义。然而，目前文献中明显缺乏对结直肠癌（CRC）特异性血小板和凝血标志物的全面研究。因此，迫切需要进一步探索这些标志物的机制基础及其潜在的临床应用。
通过整合癌症基因组图谱中CRC患者的RNA测序数据和临床病理信息，我们使用加权基因共表达网络和单变量Cox分析确定了与血小板-凝血系统相关的基因。我们使用Lasso Cox回归分析建立了基于血小板和凝血相关基因的预后风险模型，并在两个独立的CRC队列中验证了该模型。我们通过综合生物信息学分析探索了高风险和低风险组之间潜在的生物学功能差异。
我们的研究结果表明，被归类为高风险组的CRC患者通常预后较差。此外，该模型的风险评分与免疫肿瘤微环境的差异组成相关，表明其可用于推断免疫治疗反应性。细胞功能实验和动物实验表明，CRC中CYP19A1的表达影响恶性表型和血小板活化。
总之，我们提出了一种用于CRC患者预后评估的新型血小板和凝血相关风险模型，并证实了CYP19A1在促进CRC恶性进展中的重要作用。
