Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Interventional Institute of Zhengzhou University, Zhengzhou, China.
Front Immunol. 2022 Jul 1;13:873871. doi: 10.3389/fimmu.2022.873871. eCollection 2022.
Fluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.
Firstly, Weighted gene co-expression network analysis (WGCNA) identified modules tightly associated with chemotherapy response. Then, the in-house cohort and prognostic cohorts from TCGA and GEO were subjected to Cox proportional hazards model and survival analysis to ascertain the predictable function of SCG2 on the prognosis of CRC patients. Finally, we performed experiments, functional analysis, somatic mutation, and copy number variation research to explore the biological characteristics of SCG2.
We identified red and green as the modules most associated with chemotherapy response, in which SCG2 was considered a risky factor with higher expression predicting poorer prognosis. SCG2 expression in the APC non-mutation group was remarkably higher than in the mutation group. The mutation frequencies of amplified genes differed significantly between different SCG2 expression subgroups. Besides, CRC cell lines with SCG2 knockdown have reduced invasive, proliferative, and proliferative capacity. We discovered that the SCG2 high expression subgroup was the immune hot type and considered more suitable for immunotherapy.
This study demonstrates the clinical significance and biological characteristics of SCG2, which could serve as a promising biomarker to identify patients who may benefit from chemotherapy and immunotherapy.
氟尿嘧啶（FU）为基础的化疗方案在结直肠癌（CRC）的综合治疗中不可或缺。然而，由于个体的异质性和化疗的严重不良反应，总体获益有限。
首先，采用加权基因共表达网络分析（WGCNA）鉴定与化疗反应密切相关的模块。然后，对 TCGA 和 GEO 中的内部队列和预后队列进行 Cox 比例风险模型和生存分析，以确定 SCG2 对 CRC 患者预后的预测功能。最后，我们进行了实验、功能分析、体细胞突变和拷贝数变异研究，以探讨 SCG2 的生物学特征。
我们确定红色和绿色模块与化疗反应最相关，其中 SCG2 被认为是一个风险因素，高表达预示着预后较差。APC 无突变组的 SCG2 表达明显高于突变组。不同 SCG2 表达亚组之间扩增基因的突变频率存在显著差异。此外，敲低 SCG2 的 CRC 细胞系的侵袭、增殖和增殖能力降低。我们发现，SCG2 高表达亚组是免疫热型，被认为更适合免疫治疗。
本研究表明 SCG2 具有临床意义和生物学特征，可作为识别可能受益于化疗和免疫治疗的患者的有前途的生物标志物。
