转录因子SOX12在肺腺癌中的表达及其与临床预后的关系
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摘要
目的探讨转录因子SOX12在肺腺癌中的表达及其与临床预后的关系。方法采用大型癌症基因组数据库分析SOX12在肺腺癌中的表达水平,然后分别采用免疫组织化学(IHC)和半定量PCR方法检测36例肺腺癌癌组织、15例距肿瘤边缘5 cm以上癌旁正常组织和21例正常肺组织中SOX12的表达情况,同时通过Kaplan-Meier Plotter数据库获取了866例肺腺癌患者和675例肺鳞癌患者的生存数据,分析SOX12基因表达水平对患者总生存期(OS)和进展后生存期(PPS)的影响。结果 TCGA数据库和GEO(GSE40419)样本集提示SOX12的表达水平在肺腺癌组中显著高于癌旁组(P<0.001),同时IHC和半定量PCR结果均显示SOX12在肺腺癌组织中的表达高于癌旁正常组织和正常肺组织,差异具有统计学意义(P<0.001);分析Kaplan-MeierPlotter数据库显示SOX12基因表达水平高的肺腺癌患者较表达水平低的患者OS和PPS短,差异具有统计学意义(P<0.05);而SOX12基因表达水平对肺鳞癌患者的OS和PPS均无明显影响。结论转录因子SOX12在肺腺癌组织中呈明显高表达水平,且其表达水平与患者的生存和预后关系密切,SOX12可能成为预测肺腺癌发生发展的辅助指标。
Objective To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy.Methods Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma.Immunohistochemistry(IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues,15 adjacent tissues and 21 normal lung tissues.The prognostic value of SOX12 in lung adenocarcinoma and lung squamous cell carcinoma were analyzed using Kaplan-Meier Plotter database,and the relationship between SOX12 expression and the overall survival(OS) and progression free survival(PPS) of the patients were analyzed.Results Analysis of TCGA database and GEO(GSE40419) database showed that SOX12 expression levels were significantly higher in in lung adenocarcinoma than in normal lung tissues(P<0.001).The results of IHC and semiquantitative PCR revealed that SOX12 was expressed at significantly higher levels in lung adenocarcinoma than in normal lung tissues(P<0.001).Kaplan-Meier survival analysis showed that patients with lung adenocarcinoma positive for SOX12 had a significantly shorter OS and PPS time than those negative for SOX12(P<0.05),but SOX12 positivity did not significantly affect OS and PPS of patients with lung squamous cell carcinoma.Conclusion High expression levels of SOX12 in lung adenocarcinoma are significantly associated with a poor OS of the patients,suggesting the value of SOX12 to assist in early diagnosis and prognostic evaluation of lung adenocarcinoma.
Objective To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy.Methods Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma.Immunohistochemistry(IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues,15 adjacent tissues and 21 normal lung tissues.The prognostic value of SOX12 in lung adenocarcinoma and lung squamous cell carcinoma were analyzed using Kaplan-Meier Plotter database,and the relationship between SOX12 expression and the overall survival(OS) and progression free survival(PPS) of the patients were analyzed.Results Analysis of TCGA database and GEO(GSE40419) database showed that SOX12 expression levels were significantly higher in in lung adenocarcinoma than in normal lung tissues(P<0.001).The results of IHC and semiquantitative PCR revealed that SOX12 was expressed at significantly higher levels in lung adenocarcinoma than in normal lung tissues(P<0.001).Kaplan-Meier survival analysis showed that patients with lung adenocarcinoma positive for SOX12 had a significantly shorter OS and PPS time than those negative for SOX12(P<0.05),but SOX12 positivity did not significantly affect OS and PPS of patients with lung squamous cell carcinoma.Conclusion High expression levels of SOX12 in lung adenocarcinoma are significantly associated with a poor OS of the patients,suggesting the value of SOX12 to assist in early diagnosis and prognostic evaluation of lung adenocarcinoma.
引文
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[19]Dravis C,Chung CY,Lytle NK,et al.Epigenetic and transcriptomic profiling of mammary gland development and tumor models disclose regulators of cell state plasticity[J].Cancer Cell,2018,34(3):466.
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[23]Gu WJ,Wang BH,Wan FN,et al.SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma[J].Oncol Lett,2018,15(4):4564-70.
[24]Gyffy B,Lánczky A,Szállási Z.Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients[J].Endocr Relat Cancer,2012,19(2):197-208.
[2]Liu TC,Jin X,Wang Y,et al.Role of epidermal growth factor receptor in lung cancer and targeted therapies[J].Am J Cancer Res,2017,7(2):187-202.
[3]Singh A,Settleman JE.Cancer stem cells and drug resistance:an emerging axis of evil in the war on cancer[J].Oncogene,2010,29(34):4741-51.
[4]解智慧,何炜,王峰,等.干细胞转录调控因子SOX2在食管鳞癌中的表达及其与临床预后的关系[J].西安交通大学学报:医学版,2013,34(3):361-5,370.
[5]陆思千,贾舒婷,罗瑛.突变p53功能研究新进展与个性化的肿瘤治疗新策略[J].遗传,2011,33(6):539-48.
[6]Jiang T,Hou CC,She ZY,et al.The SOX gene family:function and regulation in testis determination and male fertility maintenance[J].Mol Biol Rep,2013,40(3):2187-94.
[7]Zhu Y,Li Y,Jun Wei JW,et al.The role of Sox genes in lung morphogenesis and Cancer[J].Int J Mol Sci,2012,13(12):15767-83.
[8]Jay P,Sahly I,Goze C,et al.SOX22 is a new member of the SOXgene family,mainly expressed in human nervous tissue[J].Hum Mol Genet,1997,6(7):1069-77.
[9]Wang L,Hu FQ,Shen SE,et al.Knockdown of SOX12 expression inhibits the proliferation and metastasis of lung cancer cells[J].Am J Transl Res,2017,9(9):4003.
[10]Shiao YH,Palli D,Caporaso NE,et al.Genetic and immunohistochemical analyses of p53 independently predict regional metastasis of gastric cancers[J].Cancer Epidemiol Biomarkers Prev,2000,9(6):631-3.
[11]Charafe-Jauffret E,Tarpin C,Bardou VJ,et al.Immunophenotypic analysis of inflammatory breast cancers:identification of an'inflammatory signature[J].J Pathol,2010,202(3):265-73.
[12]Gyorffy B,Surowiak P,Budczies J,et al.Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer[J].PLoS One,2013,8(12):0082241.
[13]Travis WD,Brambilla E,Noguchi M,et al.International association for the study of lung cancer/American thoracic society/European respiratory society:international multidisciplinary classification of lung adenocarcinoma:executive summary[J].Proc Am Thorac Soc,2011,8(5):381-5.
[14]Imielinski M,Berger AH,Hammerman PS,et al.Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing[J].Cell,2012,150(6):1107-20.
[15]Ding L,Getz G,Wheeler DA,et al.Somatic mutations affect key pathways in lung adenocarcinoma[J].Nature,2008,455(7216):1069-75.
[16]Kamachi Y,Kondoh H.Sox proteins:regulators of cell fate specification and differentiation[J].Development,2013,140(20):4129-44.
[17]Wegner M.All purpose Sox:The many roles of Sox proteins in gene expression[J].Int J Biochem Cell Biol,2010,42(3):0-390.
[18]王钰婷,薛立辉,聂刘旺.SOX基因与肿瘤关系的研究进展[J].癌变·畸变·突变,2009,21(1):77-80.
[19]Dravis C,Chung CY,Lytle NK,et al.Epigenetic and transcriptomic profiling of mammary gland development and tumor models disclose regulators of cell state plasticity[J].Cancer Cell,2018,34(3):466.
[20]Duquet A,Melotti A,Mishra S,et al.A novel genome-wide in vivo screen for metastatic suppressors in human colon Cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12[J].EMBO Mol Med,2014,6(7):882-901.
[21]Huang W,Chen Z,Shang X,et al.Sox12,a direct target of FoxQ1,promotes hepatocellular carcinoma metastasis through upregulating Twist1 and FGFBP1[J].Hepatology,2015,61(6):1920-33.
[22]Ding H,Quan H,Yan W,et al.Silencing of SOX12 by shRNAsuppresses migration,invasion and proliferation of breast cancer cells[J].Biosci Rep,2016,36(5):e00389-e00389.
[23]Gu WJ,Wang BH,Wan FN,et al.SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma[J].Oncol Lett,2018,15(4):4564-70.
[24]Gyffy B,Lánczky A,Szállási Z.Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients[J].Endocr Relat Cancer,2012,19(2):197-208.