目的: 通过生物信息学分析构建肺腺癌蛋白质预后模型。方法: 从癌症蛋白质组图谱和肿瘤基因组图谱数据库分别获取肺腺癌的蛋白质数据和相应的临床数据,通过单因素 Cox 回归分析和逐步回归分析筛选与肺腺癌预后相关的蛋白质,建立预后风险模型;使用多因素 Cox 回归对其进行预后风险评分分析,计算曲线下面积(AUC)评价模型的稳健性和准确性。结果: 筛选出3个与生存显著相关的蛋白质用于预后模型的构建;预后模型风险评分与预后显著相关(P<0.001),可作为评估患者预后的独立风险因子;预后模型AUC=0.710,说明模型具有稳定的特异性和灵敏度。结论: 该预后模型能准确预测肺腺癌患者的总体生存率,有助于临床早期识别预后不良的肺腺癌患者并对其进行早期干预治疗,对提高肺腺癌的生存率具有重要意义。此外,筛选出3个促进肺腺癌进展的风险蛋白有望成为肺腺癌治疗的新靶点。
Objective: To establish the protein prognostic model for lung adenocarcinoma based on bioinformatics. Methods: The protein data and related clinical data of lung adenocarcinoma were obtained from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA) database respectively, and the proteins associated with the prognosis of lung adenocarcinoma were screened using univariate Cox regression analysis and stepwise regression to establish the prognostic risk model. The model was analyzed by prognostic risk score using multivariate Cox regression, and the area under the curve (AUC) was calculated to evaluate the robustness and accuracy of the model. Results: Three proteins significantly correlated with survival were screened for the construction of the prognostic model. The risk score of the prognostic model was significantly correlated with the prognosis (P<0.001), which could be used as an independent risk factor to evaluate the prognosis of patients. The AUC of the prognostic model was 0.710, indicating that the model had stable specificity and sensitivity. Conclusion: The prognosis model could accurately predict the overall survival rate of patients with lung adenocarcinoma, which is helpful for early identification of patients with poor prognosis of lung adenocarcinoma and early intervention treatment, and is of great significance to improve the survival rate of patients with lung adenocarcinoma. In addition, three risk proteins screened in this study that promote the progression of lung adenocarcinoma are expected to become new targets for the treatment of lung adenocarcinoma.
[1] Inamura K. Clinicopathological characteristics and mutations driving development of early lung adenocarcinoma: tumor initiation and progression[J]. Int J Mol Sci, 2018, 19(4): 1259.
[2] Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer[J]. Nature, 2018, 553(7689): 446-454.
[3] Talapatra A, Rouse R, Hardiman G. Protein microarrays: challenges and promises[J]. Pharmacogenomics, 2002, 3(4): 527-536.
[4] Kwon YW, Jo HS, Bae S, et al. Application of proteomics in cancer: recent trends and approaches for biomarkers discovery[J]. Front Med, 2021, 8: 747333.
[5] Yamada T. Quantification of biomarker proteins using reverse-phase protein arrays[J].Proteomics Clin Appl, 2020, 14(4): e1900120.
[6] Santiago L, Daniels G, Wang DW, et al. Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment [J]. Am J Cancer Res, 2017, 7(6): 1389-1406.
[7] Briones-Orta MA, Avendaño-Vázquez SE, Aparicio-Bautista DI, et al. Osteopontin splice variants and polymorphisms in cancer progression and prognosis[J]. Biochim Biophys Acta BBA Rev Cancer, 2017, 1868(1): 93-108.
[8] Mor G, Visintin I, Lai Y L, et al. Serum protein markers for early detection of ovarian cancer[J]. PNAS, 2005, 102(21): 7677-7682.
[9] Zhu CJ, Jiang L, Xu J, et al. The urokinase-type plasminogen activator and inhibitors in resectable lung adenocarcinoma[J]. Pathol Res Pract, 2020, 216(4): 152885.
[10] Placencio VR, Declerck YA. Plasminogen activator inhibitor-1 in cancer: rationale and insight for future therapeutic testing[J]. Cancer Res, 2015, 75(15): 2969-2974.
[11] Kukulj S, Jaganjac M, Boranic M, et al. Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer[J]. Med Oncol, 2010, 27(2): 268-277.
[12] Corte-Rodríguez M, Blanco-González E, Bettmer J, et al. Quantitative analysis of transferrin receptor 1 (TfR1) in individual breast cancer cells by means of labeled antibodies and elemental (ICP-MS) detection[J]. Anal Chem, 2019, 91(24): 15532-15538.
[13] 黄雅可. TFRC通过调控AXIN2表达在上皮性卵巢癌发生及侵袭转移中的作用及机制研究[D]. 重庆: 中国人民解放军陆军军医大学, 2020.
[14] Prutki M, Poljak-Blazi M, Jakopovic M, et al. Altered iron metabolism, transferrin receptor 1 and ferritin in patients with colon cancer[J]. Cancer Lett, 2006, 238(2): 188-196.
[15] Jeong SM, Hwang S, Seong RH. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation[J]. Biochem Biophys Res Commun, 2016, 471(3): 373-379.
[16] Hu CX, Yang K, Li MJ, et al. Lipocalin 2: a potential therapeutic target for breast cancer metastasis[J]. Oncotargets Ther, 2018, 11: 8099-8106.
[17] Gumpper K, Dangel AW, Pita-Grisanti V, et al. Lipocalin-2 expression and function in pancreatic diseases[J]. Pancreatology, 2020, 20(3): 419-424.
[18] Hamilton G, Rath B, Klameth L, et al. Small cell lung cancer: recruitment of macrophages by circulating tumor cells[J]. OncoImmunology, 2016, 5(3): e1093277.
[19] Du ZP, Wu BL, Xia QX, et al. LCN2-interacting proteins and their expression patterns in brain tumors[J]. Brain Res, 2019, 1720: 146304.
[20] Chiang KC, Yeh TS, Wu RC, et al. Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker[J]. Sci Reports, 2016, 6: 36138.
[21] Wang YF, Yu L, Ding J, et al. Iron metabolism in cancer[J]. Int J Mol Sci, 2018, 20(1): 95.