Femi Odekunle Florence
Department of Health Informatics, School of Health Professions Rutgers, The State University of New Jersey, USA.
Int J Health Sci (Qassim). 2018 Jan-Feb;12(1):28-32.
A number of studies indicated racial differences in cervical cancer outcomes and several factors are associated with it such as stage, comorbidities, treatment pattern, and socioeconomic status. However, the associations of tumor genomic patterns such as phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene mutations and amplifications with cervical cancer racial disparities are largely unexplored.
Therefore, the present investigation aimed to identify genetic alterations (mutations and copy number variations) in cervical cancer and determine whether the PIK3CA gene mutations and amplifications in cervical cancer differ across racial/ethnic groups in the United States.
This study made use of The Cancer Genome Atlas (TCGA) database. TCGA database is a publicly available database that was created by a joint effort between the National Cancer Institute and the National Human Genome Research Institute. The two-tailed Fisher's exact test was used to test for associations between the categorical variables, race, and PIK3CA gene mutation as well as PIK3CA gene amplification using the "Fisher test" function in R.
There were 309 cervical cancer samples, and of these, 194 samples had gene mutations and 295 samples had copy number alteration data. The top five mutated genes in TCGA dataset were PIK3CA, MUC4, KMT2C, SYNE1, and KMT2D. The top five amplified genes in TCGA dataset were MECOM, TP63, PRKCI, PIK3CA, and TRFC. The PIK3CA gene had the highest number of mutations with 53 mutation counts. The mutation rates were 62.5%, 31.3%, 25.4%, and 21.1% for American Indian, African American, White, and Asian, respectively. The amplification rates were 28.6%, 21.1%, 18.9%, and 12.5% for African American, Asian, White, and American Indian.
There are many significantly mutated or amplified genes implicated in cervical cancer. Some of them are not grouped with the already known genes in relation to cervical cancer. For example, the KMT2C, SYNE1, KMT2D, EP300, RYR2, FLG, DMD, FBXW, MECOM, TRFC, RPL35A, LPP, TBL, FGF12, and SOX2 genes. They can be explored as therapeutic targets to improve cervical cancer treatment.
多项研究表明宫颈癌的治疗结果存在种族差异，且有几个因素与之相关，如分期、合并症、治疗模式和社会经济地位。然而，诸如磷脂酰肌醇3-激酶催化亚基α（PIK3CA）基因突变和扩增等肿瘤基因组模式与宫颈癌种族差异之间的关联在很大程度上尚未得到探索。
因此，本研究旨在识别宫颈癌中的基因改变（突变和拷贝数变异），并确定美国不同种族/族裔群体宫颈癌中PIK3CA基因突变和扩增情况是否存在差异。
本研究利用了癌症基因组图谱（TCGA）数据库。TCGA数据库是一个公开可用的数据库，由美国国立癌症研究所和国家人类基因组研究所共同创建。使用R语言中的“Fisher检验”函数，采用双尾Fisher精确检验来检验分类变量、种族与PIK3CA基因突变以及PIK3CA基因扩增之间的关联。
共有309份宫颈癌样本，其中194份样本有基因突变，295份样本有拷贝数改变数据。TCGA数据集中前五个突变基因是PIK3CA、MUC4、KMT2C、SYNE1和KMT2D。TCGA数据集中前五个扩增基因是MECOM、TP63、PRKCI、PIK3CA和TRFC。PIK3CA基因的突变数最多，有53个突变计数。美国印第安人、非裔美国人、白人和亚洲人的突变率分别为62.5%、31.3%、25.4%和21.1%。非裔美国人、亚洲人、白人和美国印第安人的扩增率分别为28.6%、21.1%、18.9%和12.5%。
宫颈癌中有许多显著突变或扩增的基因。其中一些基因与宫颈癌中已知基因的类别不同。例如，KMT2C、SYNE1、KMT2D、EP300、RYR2、FLG、DMD、FBXW、MECOM、TRFC、RPL35A、LPP、TBL、FGF12和SOX2基因。它们可作为改善宫颈癌治疗的治疗靶点进行探索。
