基于生物信息学技术探讨宫颈癌肿瘤组织中p53突变、共表达网络及临床转归分析
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摘要
目的利用生物信息学技术探讨p53在宫颈癌的突变、共表达网络及在疾病预后中的预测能力,为宫颈癌的诊断与预后判断提供一定的理论基础。方法利用癌症基因组图谱数据库对靶标分子p53进行检索,发现其突变及可能的作用分子与网络。结果 p53基因在宫颈癌中的突变率约为9%,通过STRING在线数据库找到在宫颈癌中与p53互作分子Bcl2,p53的表达水平与宫颈癌预后呈正相关。结论本研究发现了与p53共同发挥生物学功能的相关分子Bcl2,为宫颈癌的早期诊断、靶向治疗及预后判断提供了一定理论基础。
Objective To explore the role of p53 for its mutation, co-expression network and its prognostic ability in cervical cancer, and to provide a theoretical basis for the diagnosis and prognosis of cervical cancer. Methods The target molecule p53 was searched using The Cancer Genome Atlas(TCGA) database to identify its mutations, possible molecules and networks. Results The mutation rate of p53 gene in cervical cancer was about 9%. The expression level of p53 interacting molecule Bcl2 and p53 in cervical cancer is positively correlated with the prognosis of cervical cancer in STRING database. Conclusion This study showes that Bcl2 may play an important biological role together with p53 in cervical cancer, by which to provide a theoretical basis for early diagnosis, targeted therapy and prognosis of cervical cancer.
Objective To explore the role of p53 for its mutation, co-expression network and its prognostic ability in cervical cancer, and to provide a theoretical basis for the diagnosis and prognosis of cervical cancer. Methods The target molecule p53 was searched using The Cancer Genome Atlas(TCGA) database to identify its mutations, possible molecules and networks. Results The mutation rate of p53 gene in cervical cancer was about 9%. The expression level of p53 interacting molecule Bcl2 and p53 in cervical cancer is positively correlated with the prognosis of cervical cancer in STRING database. Conclusion This study showes that Bcl2 may play an important biological role together with p53 in cervical cancer, by which to provide a theoretical basis for early diagnosis, targeted therapy and prognosis of cervical cancer.
引文
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[8]Hietanen S,Lain S,Krausz E,et al.Activation of p53 in cervical carcinoma cells by small molecules.Proc Natl Acad Sci U S A,2000,97(15):8501-8506.
[9]Small W Jr,Bacon MA,Bajaj A,et al.Cervical cancer:a global health crisis.Cancer,2017,123(13):2404-2412.
[10]Molinolo AA,Marsh C,El Dinali M,et al.m TOR as a molecular target in HPV-associated oral and cervical squamous carcinomas.Clin Cancer Res,2012,18(9):2558-2568.
[11]Ferenczy A,Franco E.Persistent human papillomavirus infection and cervical neoplasia.Lancet Oncol,2002,3(1):11-16.
[12]Co NN,Iglesias D,Celestino J,et al.Loss of LKB1 in high-grade endometrial carcinoma:LKB1 is a novel transcriptional target of p53.Cancer,2014,120(22):3457-3468.
[13]Kumar R,Sharma A,Kumari A,et al.Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway.Biogerontology,2018.[Epub ahead of print]
[14]Liao W,Liu J,Liu B,et al.JIB04 induces cell apoptosis via activation of the p53/Bcl2/caspase pathway in MHCC97H and HepG2 cells.Oncol Rep,2018,40(6):3812-3820.
[15]Roy S,Sil A,Chakraborty T.Potentiating apoptosis and modulation of p53,Bcl2,and Bax by a novel chrysin ruthenium complex for effective chemotherapeutic efficacy against breast cancer.J Cell Physiol,2019,234(4):4888-4909.
[2]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012.CACancer J Clin,2015,65(2):87-108.
[3]Ramanathan P,Dhandapani H,Jayakumar H,et al.Immunotherapy for cervical cancer:can it do another lung cancer?Curr Probl Cancer,2018,42(2):148-160.
[4]Amini A,Robin TP,Stumpf PK,et al.Rising rates of upfront surgery in early locally advanced cervical cancer:What factors predict for this treatment paradigm?Int J Gynecol Cancer,2018,28(8):1560-1568.
[5]Zhao Y,Wu L,Yue X,et al.A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models.Elife,2018,7:e34701.
[6]Cancer Genome Atlas Research N,Weinstein JN,Collisson EA,et al.The cancer genome atlas pan-cancer analysis project.Nat Genet,2013,45(10):1113-1120.
[7]Gao J,Aksoy BA,Dogrusoz U,et al.Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.Sci Signal,2013,6(269):pl1.
[8]Hietanen S,Lain S,Krausz E,et al.Activation of p53 in cervical carcinoma cells by small molecules.Proc Natl Acad Sci U S A,2000,97(15):8501-8506.
[9]Small W Jr,Bacon MA,Bajaj A,et al.Cervical cancer:a global health crisis.Cancer,2017,123(13):2404-2412.
[10]Molinolo AA,Marsh C,El Dinali M,et al.m TOR as a molecular target in HPV-associated oral and cervical squamous carcinomas.Clin Cancer Res,2012,18(9):2558-2568.
[11]Ferenczy A,Franco E.Persistent human papillomavirus infection and cervical neoplasia.Lancet Oncol,2002,3(1):11-16.
[12]Co NN,Iglesias D,Celestino J,et al.Loss of LKB1 in high-grade endometrial carcinoma:LKB1 is a novel transcriptional target of p53.Cancer,2014,120(22):3457-3468.
[13]Kumar R,Sharma A,Kumari A,et al.Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway.Biogerontology,2018.[Epub ahead of print]
[14]Liao W,Liu J,Liu B,et al.JIB04 induces cell apoptosis via activation of the p53/Bcl2/caspase pathway in MHCC97H and HepG2 cells.Oncol Rep,2018,40(6):3812-3820.
[15]Roy S,Sil A,Chakraborty T.Potentiating apoptosis and modulation of p53,Bcl2,and Bax by a novel chrysin ruthenium complex for effective chemotherapeutic efficacy against breast cancer.J Cell Physiol,2019,234(4):4888-4909.