Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
BMC Pulm Med. 2022 Dec 6;22(1):467. doi: 10.1186/s12890-022-02269-4.
Tripartite motif (TRIM) family genes get involved in the pathogenesis and development of various biological processes; however, the prognostic value of TRIM genes for idiopathic pulmonary fibrosis (IPF) needs to be explored.
We acquired gene expression based on bronchoalveolar lavage (BAL) cells and clinical data of three independent IPF cohorts in the GSE70866 dataset from the Gene expression omnibus (GEO) database. Differentially expressed TRIM genes (DETGs) between IPF patients and healthy donors were identified and used to establish a risk signature by univariate and multivariate Cox regression analysis in the training cohort. The risk signature was further validated in other IPF cohorts, and compared with previously published signatures. Moreover, we performed functional enrichment analysis to explore the potential mechanisms. Eventually, the quantitative real time PCR was conducted to validate the expressions of the key genes in BAL from 12 IPF patients and 12 non-IPF controls from our institution.
We identified 4 DETGs including TRIM7, MEFV, TRIM45 and TRIM47 significantly associated with overall survival (OS) of IPF patients (P < 0.05). A multiple stepwise Cox regression analysis was performed to construct a 4-TRIM-gene prognostic signature. We categorized IPF patients into one low-risk group and the other high-risk group as per the average risk value of the TRIM prognostic signature in the training and validation cohorts. The IPF individuals in the low-risk group demonstrated an obvious OS advantage compared with the high-risk one (P < 0.01). The time-dependent receiver operating characteristic approach facilitated the verification of the predictive value of the TRIM prognostic signature in the training and validation cohorts, compared with other published signatures. A further investigation of immune cells and IPF survival displayed that higher proportion of resting memory CD4+ T cells and resting mast cells harbored OS advantage over lower proportion, however lower proportion of neutrophils, activated dendritic cells and activated NK cells indicated worse prognosis.
The TRIM family genes are significant for the prognosis of IPF and our signature could serve as a robust model to predict OS.
三基序（TRIM）家族基因参与各种生物学过程的发病机制和发展；然而，TRIM 基因对特发性肺纤维化（IPF）的预后价值仍需探索。
我们从基因表达综合数据库（GEO）数据库中获取了基于支气管肺泡灌洗液（BAL）细胞和三个独立的 IPF 队列的临床数据的基因表达谱，并在训练队列中通过单变量和多变量 Cox 回归分析确定了 IPF 患者和健康供体之间差异表达的 TRIM 基因（DETGs）。然后，我们进一步在其他 IPF 队列中验证了该风险特征，并与之前发表的特征进行了比较。此外，我们进行了功能富集分析以探索潜在的机制。最后，我们使用来自我们机构的 12 名 IPF 患者和 12 名非 IPF 对照者的 BAL 进行了定量实时 PCR，以验证关键基因的表达。
我们确定了 4 个与 IPF 患者总生存率（OS）显著相关的 DETG，包括 TRIM7、MEFV、TRIM45 和 TRIM47（P<0.05）。我们进行了多步 Cox 回归分析，以构建一个 4-TRIM 基因预后特征。我们根据训练和验证队列中 TRIM 预后特征的平均风险值，将 IPF 患者分为低风险组和高风险组。低风险组的 IPF 患者的 OS 明显优于高风险组（P<0.01）。时间依赖性接受者操作特征曲线分析有助于验证 TRIM 预后特征在训练和验证队列中的预测价值，优于其他已发表的特征。进一步研究免疫细胞和 IPF 生存情况显示，静止记忆 CD4+T 细胞和静止肥大细胞的比例较高预示着更好的 OS，而中性粒细胞、活化树突状细胞和活化 NK 细胞的比例较低则预示着更差的预后。
TRIM 家族基因对 IPF 的预后有重要意义，我们的特征可以作为预测 OS 的强大模型。
