Department of Orthopedics, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Department of Orthopedics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
PLoS One. 2023 Jun 2;18(6):e0286647. doi: 10.1371/journal.pone.0286647. eCollection 2023.
Intervertebral disc degeneration (IDD) is a progressive chronic condition that commonly causes low back pain. Cancer is among the primary reasons for deaths worldwide. Our purpose was to identify the characteristic genes of IDD and explore the potential association between IDD and cancer.
Immune cell infiltration and differentially expressed analysis were conducted utilizing data from the GSE124272 database. Enrichment analysis of differentially expressed genes (DEGs) was performed to explore the possible mechanisms underlying IDD development. Moreover, weighted gene correlation network analysis (WGCNA) was applied to select IDD-related hub genes. The immune-related key genes were determined by intersecting DEGs, IDD-related hub genes, and immune genes. Subsequently, machine learning models based on these genes were built to identify and verify the characteristic genes. RNA sequencing and clinical data of 33 carcinoma categories were obtained from the Cancer Genome Atlas (TCGA). The association between NAIP expression and prognosis was calculated using the Kaplan-Meier analysis. To gain a deeper understanding of the impact of NAIP in tumor immunotherapy, the association between NAIP and immune infiltration and two immunotherapeutic biomarkers were explored. Ultimately, the association between NAIP and immunotherapeutic response was investigated utilizing two independent cohorts.
NAIP was identified as an immune-related characteristic gene between IDD and normal intervertebral disc tissue. In certain carcinoma categories, NAIP expression levels were elevated (4/33) and significantly correlated to the respective tumor stage (4/21). Survival analysis revealed that the expression levels of NAIP have prognostic significance in different cancer types. Generally, NAIP presented a strong association with immune cell infiltration and modulators. NAIP may influence immunotherapy effects through tumor mutational burden and microsatellite instability. No remarkable association between NAIP and immunotherapy response was found in either cohort.
Our study is the first to identify NAIP as an immune-related characteristic gene. Pan-cancer analysis revealed that NAIP could serve as a novel clinical prognostic marker and therapeutic target for a variety of carcinoma categories, reducing the risk of IDD in tumor patients.
椎间盘退行性病变（IDD）是一种常见的慢性进行性疾病，常引起下腰痛。癌症是全球主要死亡原因之一。我们的目的是确定 IDD 的特征基因，并探讨 IDD 与癌症之间的潜在关联。
利用 GSE124272 数据库中的数据进行免疫细胞浸润和差异表达分析。对差异表达基因（DEGs）进行富集分析，以探讨 IDD 发生发展的可能机制。此外，应用加权基因相关网络分析（WGCNA）选择与 IDD 相关的枢纽基因。通过交集 DEGs、与 IDD 相关的枢纽基因和免疫基因来确定免疫相关关键基因。随后，基于这些基因构建机器学习模型，以识别和验证特征基因。从癌症基因组图谱（TCGA）中获取 33 种癌种的 RNA 测序和临床数据。利用 Kaplan-Meier 分析计算 NAIP 表达与预后的关系。为了更深入地了解 NAIP 对肿瘤免疫治疗的影响，探索了 NAIP 与免疫浸润和两种免疫治疗生物标志物的关系。最终，利用两个独立的队列研究了 NAIP 与免疫治疗反应的关系。
NAIP 被鉴定为 IDD 与正常椎间盘组织之间的免疫相关特征基因。在某些癌种中，NAIP 的表达水平升高（4/33），且与相应的肿瘤分期显著相关（4/21）。生存分析表明，NAIP 的表达水平在不同癌症类型中具有预后意义。一般来说，NAIP 与免疫细胞浸润和调节剂呈强相关。NAIP 可能通过肿瘤突变负荷和微卫星不稳定性影响免疫治疗效果。在两个队列中，均未发现 NAIP 与免疫治疗反应之间存在显著关联。
本研究首次将 NAIP 鉴定为免疫相关特征基因。泛癌分析表明，NAIP 可以作为多种癌种的新型临床预后标志物和治疗靶点，降低肿瘤患者发生 IDD 的风险。
