Zhang Lina, Liu Chengyu, Zhang Xiaochong, Wang Changjing, Liu Dengxiang
Department of Health Examination Center, Xingtai People's Hospital, Xingtai, 054001, Hebei, China.
Graduate School of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Funct Integr Genomics. 2023 Apr 4;23(2):117. doi: 10.1007/s10142-023-01026-y.
According to statistics, breast cancer (BC) has replaced lung cancer as the most common cancer in the world. Therefore, specific detection markers and therapeutic targets need to be explored as a way to improve the survival rate of BC patients. We first identified m6A/m5C/m1A/m7G-related long noncoding RNAs (MRlncRNAs) and developed a model of 16 MRlncRNAs. Kaplan-Meier survival analysis was applied to assess the prognostic power of the model, while univariate Cox analysis and multivariate Cox analysis were used to assess the prognostic value of the constructed model. Then, we constructed a nomogram to illustrate whether the predicted results were in good agreement with the actual outcomes. We tried to use the model to distinguish the difference in sensitivity to immunotherapy between the two groups and performed some analyses such as immune infiltration analysis, ssGSEA and IC50 prediction. To explore the novel anti-tumor drug response, we reclassified the patients into two clusters. Next, we assessed their response to clinical treatment by the R package pRRophetic, which is determined by the IC50 of each BC patient. We finally identified 11 MRlncRNAs and based on them, a risk model was constructed. In this model, we found good agreement between calibration plots and prognosis prediction. The AUC of ROC curves was 0.751, 0.734, and 0.769 for 1-year, 2-year, and 3-year overall survival (OS), respectively. The results showed that the IC50 was significantly different between the risk groups, suggesting that the risk groups can be used as a guide for systemic treatment. We regrouped patients into two clusters based on 11 MRlncRNAs expression. Next, we conducted immune scores for 2 clusters, which showed that cluster 1 had higher stromal scores, immune scores and higher estimated (microenvironment) scores, demonstrating that TME of cluster 1 was different from cluster 2. The results of this study support that MRlncRNAs can predict tumor prognosis and help differentiate patients with different sensitivities to immunotherapy as a basis for individualized treatment for BC patients.
据统计,乳腺癌(BC)已取代肺癌成为全球最常见的癌症。因此,需要探索特异性检测标志物和治疗靶点,以提高BC患者的生存率。我们首先鉴定了m6A/m5C/m1A/m7G相关长链非编码RNA(MRlncRNAs),并构建了一个包含16个MRlncRNAs的模型。应用Kaplan-Meier生存分析评估该模型的预后能力,同时采用单因素Cox分析和多因素Cox分析评估所构建模型的预后价值。然后,我们构建了一个列线图,以说明预测结果与实际结果是否高度一致。我们尝试使用该模型区分两组对免疫治疗敏感性的差异,并进行了免疫浸润分析、单样本基因集富集分析(ssGSEA)和半数抑制浓度(IC50)预测等分析。为了探索新型抗肿瘤药物反应,我们将患者重新分为两个聚类。接下来,我们通过R包pRRophetic评估他们对临床治疗的反应,该反应由每个BC患者的IC50决定。我们最终鉴定出11个MRlncRNAs,并基于它们构建了一个风险模型。在这个模型中,我们发现校准曲线与预后预测之间具有良好的一致性。1年、2年和3年总生存期(OS)的受试者工作特征曲线(ROC)的曲线下面积(AUC)分别为0.751、0.734和0.769。结果表明,风险组之间的IC50存在显著差异,这表明风险组可作为全身治疗的指导。我们根据11个MRlncRNAs的表达将患者重新分为两个聚类。接下来,我们对两个聚类进行免疫评分,结果显示聚类1具有更高的基质评分、免疫评分和更高的估计(微环境)评分,表明聚类1的肿瘤微环境(TME)与聚类2不同。本研究结果支持MRlncRNAs可预测肿瘤预后,并有助于区分对免疫治疗具有不同敏感性的患者,作为BC患者个体化治疗的依据。