Li Tao, Liu Peilong, Wang Yan, Xu Hong
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, China.
J Thorac Dis. 2025 Aug 31;17(8):6112-6126. doi: 10.21037/jtd-2025-1273. Epub 2025 Aug 20.
Neuron-related cell adhesion molecule (NrCAM) has been implicated in tumor progression, but its role in small-cell lung cancer (SCLC) remains unclear. This study examined the clinical significance of NrCAM in SCLC and its impact on cellular processes.
Differentially expressed genes (DEGs) in SCLC were identified from The Cancer Genome Atlas (TCGA) datasets (GSE6044, GSE111044, and GSE44447) according to a |log fold change (FC)| >2 and a P value <0.05. Clinical and pathological data, along with tumor tissue samples, were obtained from 43 patients with SCLC treated at Nantong Tumor Hospital from 2017 to 2019. NrCAM expression was analyzed via immunohistochemistry. knockdown or overexpression models were established in SCLC cell lines to evaluate proliferation, colony formation, migration, and invasion . A xenograft mouse model was used to assess NrCAM's effects .
Immunohistochemical analysis revealed higher NrCAM expression in SCLC tissues as compared to adjacent noncancerous tissues. Patients with high NrCAM expression exhibited shorter survival (P=0.04) and significant associations with tumor-node-metastasis (TNM) stage, tumor size, and differentiation grade (P<0.05). Multivariate Cox analysis identified high NrCAM expression as an independent risk factor for poor prognosis (P=0.04). knockdown significantly inhibited SCLC cell proliferation, migration, and invasion (P<0.05), while overexpression resulted in the opposite effects. In the xenograft model, NrCAM knockdown reduced tumor volume and Ki-67 expression (P<0.05).
NrCAM overexpression in SCLC is associated with poor prognosis. Knockdown of expression inhibited the proliferation, migration, and invasion of SCLC cells, suggesting that could be a potential biomarker for diagnosis and prognostic evaluation in SCLC.
神经元相关细胞粘附分子（NrCAM）与肿瘤进展有关，但其在小细胞肺癌（SCLC）中的作用仍不清楚。本研究探讨了NrCAM在SCLC中的临床意义及其对细胞过程的影响。
根据|log倍数变化（FC）|>2和P值<0.05，从癌症基因组图谱（TCGA）数据集（GSE6044、GSE111044和GSE44447）中鉴定SCLC中的差异表达基因（DEG）。收集2017年至2019年在南通肿瘤医院接受治疗的43例SCLC患者的临床和病理数据以及肿瘤组织样本。通过免疫组织化学分析NrCAM表达。在SCLC细胞系中建立敲低或过表达模型，以评估增殖、集落形成、迁移和侵袭能力。使用异种移植小鼠模型评估NrCAM的作用。
免疫组织化学分析显示，与相邻非癌组织相比，SCLC组织中NrCAM表达更高。NrCAM高表达的患者生存期较短（P=0.04），且与肿瘤-淋巴结-转移（TNM）分期、肿瘤大小和分化程度显著相关（P<0.05）。多因素Cox分析确定NrCAM高表达是预后不良的独立危险因素（P=0.04）。敲低显著抑制SCLC细胞的增殖、迁移和侵袭（P<0.05），而过表达则产生相反的效果。在异种移植模型中，NrCAM敲低减少了肿瘤体积和Ki-67表达（P<0.05）。
SCLC中NrCAM过表达与预后不良相关。敲低NrCAM表达可抑制SCLC细胞的增殖、迁移和侵袭，提示NrCAM可能是SCLC诊断和预后评估的潜在生物标志物。
