First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
Sci Rep. 2024 Apr 17;14(1):8879. doi: 10.1038/s41598-024-59130-3.
There has been increasing interest in the role of epigenetic modification in cancers recently. Among the various modifications, sialylation has emerged as a dominant subtype implicated in tumor progression, metastasis, immune evasion, and chemoresistance. The prognostic significance of sialylation-related molecules has been demonstrated in colorectal cancer. However, the potential roles and regulatory mechanisms of sialylation in lung adenocarcinoma (LUAD) have not been thoroughly investigated. Through Pearson correlation, univariate Cox hazards proportional regression, and random survival forest model analyses, we identified several prognostic long non-coding RNAs (lncRNAs) associated with aberrant sialylation and tumor progression, including LINC00857, LINC00968, LINC00663, and ITGA9-AS1. Based on the signatures of four lncRNAs, we classified patients into two clusters with different landscapes using a non-negative matrix factorization approach. Collectively, patients in Cluster 1 (C1) exhibited worse prognoses than those in Cluster 2 (C2), as well as heavier tumor mutation burden. Functional enrichment analysis showed the enrichment of several pro-tumor pathways in C1, differing from the upregulated Longevity and programmed cell death pathways in C2. Moreover, we profiled immune infiltration levels of important immune cell lineages in two subgroups using MCPcounter scores and single sample gene set enrichment analysis scores, revealing a relatively immunosuppressive microenvironment in C1. Risk analysis indicated that LINC00857 may serve as a pro-tumor regulator, while the other three lncRNAs may be protective contributors. Consistently, we observed upregulated LINC00857 in C1, whereas increased expressive levels of LINC00968, LINC00663, and ITGA9-AS1 were observed in C2. Finally, drug sensitivity analysis suggested that patients in the two groups may benefit from different therapeutic strategies, contributing to precise treatment in LUAD. By integrating multi-omics data, we identified four core sialylation-related lncRNAs and successfully established a prognostic model to distinguish patients with different characterizations. These findings may provide some insights into the underlying mechanism of sialylation, and offer a new stratification way as well as clinical guidance in LUAD.
最近，人们对表观遗传修饰在癌症中的作用越来越感兴趣。在各种修饰中，唾液酸化作为一种主要的亚型，与肿瘤的进展、转移、免疫逃逸和化疗耐药有关。唾液酸化相关分子在结直肠癌中的预后意义已得到证实。然而，唾液酸化在肺腺癌（LUAD）中的潜在作用和调控机制尚未得到深入研究。通过 Pearson 相关性分析、单因素 Cox 风险比例回归分析和随机生存森林模型分析，我们确定了几个与异常唾液酸化和肿瘤进展相关的预后长链非编码 RNA（lncRNA），包括 LINC00857、LINC00968、LINC00663 和 ITGA9-AS1。基于这四个 lncRNA 的特征，我们使用非负矩阵分解方法将患者分为两个具有不同特征的聚类。总的来说，聚类 1（C1）的患者预后比聚类 2（C2）差，肿瘤突变负担也更重。功能富集分析表明，C1 中富集了几个促进肿瘤的途径，与 C2 中上调的长寿和程序性细胞死亡途径不同。此外，我们使用 MCPcounter 评分和单样本基因集富集分析评分在两个亚组中对重要免疫细胞谱系的免疫浸润水平进行了分析，结果表明 C1 中存在相对免疫抑制的微环境。风险分析表明，LINC00857 可能作为一种促进肿瘤的调节剂，而其他三个 lncRNA 可能是保护性贡献者。一致地，我们观察到 C1 中 LINC00857 的表达上调，而 LINC00968、LINC00663 和 ITGA9-AS1 的表达水平在 C2 中增加。最后，药物敏感性分析表明，两组患者可能受益于不同的治疗策略，有助于 LUAD 的精准治疗。通过整合多组学数据，我们确定了四个核心唾液酸化相关 lncRNA，并成功建立了一个预后模型来区分具有不同特征的患者。这些发现可能为唾液酸化的潜在机制提供一些见解，并为 LUAD 提供一种新的分层方法和临床指导。
