Zhao Huihui, Lu Guojun
Department of Oncology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Respiratory Medicine, Nanjing Chest Hospital, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.
Front Genet. 2022 Jun 8;13:905581. doi: 10.3389/fgene.2022.905581. eCollection 2022.
Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 () is involved in many human cancers. However, its clinical significance and function in lung adenocarcinoma remain unclear. Here, we examined the prognostic and immunological role of in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) was conducted to analyze expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of on survival. cBioPortal database was conducted to identify the mutation characteristics of . Functional enrichment was performed to determine -related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of at single-cell resolution. related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between expression and tumor-infiltrating lymphocytes (TILs). Both mRNA and protein expression of were significantly elevated in lung adenocarcinoma. High expression of was significantly correlated with high T stage ( = 0.014), lymph node metastases ( < 0.001), and TNM stage = 0.005). Kaplan-Meier curves indicated that high expression of was correlated with poor overall survival (38.2 vs. 59.7 months, < 0.001) and disease-specific survival (59.9 months vs. not available, = 0.004). Multivariate analysis suggested that was an independent biomarker for poor overall survival (HR 1.471, 95%CI, 1.024-2.114, = 0.037). had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma. Functional enrichment suggested expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that expression was correlated with immune cell infiltration levels and abundance of TILs. The upregulation of is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma. Our findings suggest that is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.
尽管先前的研究报道26S蛋白酶体非ATP酶调节亚基2（）参与多种人类癌症。然而，其在肺腺癌中的临床意义和功能仍不清楚。在此，我们研究了在肺腺癌中的预后和免疫作用。利用癌症基因组图谱（TCGA）分析表达情况，并使用UALCAN进行验证。使用PrognoScan和Kaplan-Meier曲线评估对生存的影响。利用cBioPortal数据库确定的突变特征。进行功能富集以确定相关功能。使用癌症单细胞状态图谱（CancerSEA）以单细胞分辨率探索的癌症功能状态。进行相关免疫浸润分析。利用肿瘤-免疫系统相互作用数据库（TISIDB）验证表达与肿瘤浸润淋巴细胞（TILs）之间的相关性。在肺腺癌中，的mRNA和蛋白表达均显著升高。的高表达与高T分期（=0.014）、淋巴结转移（<0.001）和TNM分期（=0.005）显著相关。Kaplan-Meier曲线表明，的高表达与总体生存期较差（38.2个月对59.7个月，<0.001）和疾病特异性生存期较差（59.9个月对无数据，=0.004）相关。多变量分析表明，是总体生存期较差的独立生物标志物（HR 1.471，95%CI，1.024 - 2.114，=0.037）。在肺腺癌中的突变频率较高，为14%。的基因突变也与肺腺癌的总体生存期较差、疾病特异性生存期较差和无进展生存期相关。功能富集表明表达参与细胞周期、RNA转运和细胞衰老。CancerSEA分析表明表达与细胞周期、DNA损伤和DNA修复呈正相关。免疫浸润分析表明表达与免疫细胞浸润水平和TILs丰度相关。的上调与肺腺癌的预后不良和免疫浸润水平显著相关。我们的研究结果表明，是肺腺癌预后不良的潜在生物标志物和免疫治疗靶点。
