NCAPH表达异常介导肺腺癌病人更差预后

    Study on the abnormal NCAPH expression mediating the worse prognosis in lung adenocarcinoma patients

    • 摘要:
      目的: 非SMC凝聚素I复合物亚基H(NCAPH)在多种实体癌症中发挥促癌作用。然而在肺腺癌(LUAD)的生物学功能和免疫细胞浸润作用仍不清楚。
      方法: 选取手术治疗的45例LUAD病人并采集45例LUAD组织和45例相邻正常肺组织标本。通过综合生物信息学方法分析NCAPH在LUAD中表达、生物学功能及预后价值。通过免疫印迹实验和免疫组织化学(IHC)染色分析验证NCAPH表达和预后价值。通过MTT、克隆形成、划痕和侵袭实验探索敲降NCAPH对LUAD细胞进展影响。基于TCGA数据库构建预测LUAD病人预后的Nomogram。
      结果: NCAPH定位于胞质溶胶和核质,其miRNA和蛋白质在LUAD组织中表达上调(P < 0.05)。NCAPH高表达LUAD病人总体生存率低于低表达病人(P < 0.05)。NCAPH与血管生成(r = 0.201)、炎症反应(r = 0.212)、肿瘤炎症(r = 0.185)、肿瘤增殖(r = 0.910)和EMT(r = 0.182)信号通路活性分数呈正相关关系(P < 0.05),与细胞凋亡呈负相关关系(r = –0.216,P < 0.05)。NCAPH与记忆B细胞(r = –0.327)和活化肥大细胞(r = –0.477)呈中等相关关系(P < 0.05)。高记忆B细胞浸润丰度病人具有更高的生存率(P < 0.05)。NCAPH可以独立于年龄、性别、分期和吸烟与LUAD病人死亡风险相关(P < 0.05)。敲降NCAPH能抑制LUAD细胞活力,克隆形成、迁移和侵袭能力(P < 0.05)。基于NCAPH、年龄和肿瘤分期的Nomogram指标能有效预测LUAD病人生存率且能提高显著意义的临床净收益。
      结论: NCAPH作为促癌基因,通过多种生物学途径和作用介导LUAD病人更差预后。评估和定位NCAPH有助于LUAD诊断、治疗及评估预后。

       

      Abstract:
      Objective To explore the biological functions and immune cell infiltration effects of non-SMC agglutinin I complex subunit H (NCAPH) in lung adenocarcinoma (LUAD).
      Methods Forty-five LUAD patients treated with surgery were selected, and 45 specimens of LUAD tissues and 45 adjacent normal lung tissues were collected. The expression, biological functions and prognostic value of NCAPH in LUAD were analyzed by comprehensive bioinformatics methods. The expression and prognostic value of NCAPH were verified by Western blotting and immunohistochemical (IHC) staining analysis. The effects of knocking down NCAPH on the progression of LUAD cells was explored through MTT, clone formation, scratch and invasion experiments. A Nomogram for predicting the prognosis of LUAD patients was constructed based on the TCGA database.
      Results NCAPH was located in the cytosol and nuclear cytoplasm, and its miRNA and protein expressions were upregulated in LUAD tissues (P < 0.05). The overall survival rate of LUAD patients with high NCAPH expression was lower than that of patients with low NCAPH expression (P < 0.05). NCAPH was positively correlated with the angiogenesis (r = 0.201), inflammatory response (r = 0.212), tumor inflammation (r = 0.185), tumor proliferation (r = 0.910), and activity scores of EMT signaling pathways (r = 0.182) (P < 0.05), and negatively correlated with the apoptosis (r = –0.216, P < 0.05). NCAPH was moderately correlated with the memory B cells (r = –0.327) and activated mast cells (r = –0.477) (P < 0.05). Patients with high abundance of memory B cell infiltration had a higher survival rate (P < 0.05). NCAPH was independently associated with the risk of death in LUAD patients regardless of age, gender, stage and smoking (P < 0.05). Knocking down NCAPH could inhibit the viability, clone formation, migration and invasion abilities of LUAD cells (P < 0.05). Nomogram indicators based on NCAPH, age and tumor stage could effectively predict the survival rate of LUAD patients, and significantly increase the clinical net benefit.
      Conclusions As an oncogene, NCAPH mediates a poorer prognosis for LUAD patients through multiple biological pathways and functions. Evaluating and locating NCAPH is helpful for the diagnosis, treatment and prognosis assessment of LUAD.

       

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