Hu Yibo, Jiang Ling, Lei Li, Luo Liping, Guo Haoran, Zhou Ying, Huang Jinhua, Chen Jing, Zeng Qinghai
Department of Dermatology, Third Xiangya Hospital, Central South University, No.138 Tongzipo Road, Changsha, Hunan 410013, China.
Fundam Res. 2021 Oct 29;2(1):166-176. doi: 10.1016/j.fmre.2021.08.020. eCollection 2022 Jan.
Psoriasis is a common inflammatory skin disease that seriously affects the patient's quality of life. The diagnosis of psoriasis is mainly based on clinical and pathological features, and the assessment depends on the psoriasis area and severity index (PASI). However, there are few reliable and accurate evaluation methods to assess lesion severity and therapeutic effects. This work identified 17 model genes from GEO datasets and established 6 psoriasis evaluation models by LASSO regression, linear regression, and random forest separately. Models were trained and evaluated in different GEO datasets. All 6 models accurately classified psoriatic lesions and non-lesional skin in training and testing data, and showed good AUC. In biologics-treated samples, the model scores were positively correlated with the severity of lesions and negatively correlated with treatment length. Thus, models have the potential to assess the therapeutic effects. In addition, the expression of model genes was examined in keratinocytes, skin of IMQ-induced psoriatic mice, and lesions of psoriasis patients. The RNA and protein levels of model genes increased in cytokine-stimulated keratinocytes and psoriatic lesions as expected. This work provides new methods to assess the lesion severity and therapeutic effects of biologics in psoriasis.
银屑病是一种常见的炎症性皮肤病,严重影响患者的生活质量。银屑病的诊断主要基于临床和病理特征,评估则依赖于银屑病面积和严重程度指数(PASI)。然而,目前用于评估皮损严重程度和治疗效果的可靠且准确的评估方法较少。这项研究从基因表达综合数据库(GEO)数据集中鉴定出17个模型基因,并分别通过套索回归、线性回归和随机森林建立了6种银屑病评估模型。这些模型在不同的GEO数据集中进行训练和评估。所有6个模型在训练和测试数据中都能准确区分银屑病皮损和非皮损皮肤,且表现出良好的曲线下面积(AUC)。在生物制剂治疗的样本中,模型评分与皮损严重程度呈正相关,与治疗时长呈负相关。因此,这些模型具有评估治疗效果的潜力。此外,还在角质形成细胞、咪喹莫特诱导的银屑病小鼠皮肤以及银屑病患者皮损中检测了模型基因的表达。正如预期的那样,在细胞因子刺激的角质形成细胞和银屑病皮损中,模型基因的RNA和蛋白质水平均升高。这项研究为评估生物制剂在银屑病中的皮损严重程度和治疗效果提供了新方法。