Uterine cervical carcinoma (CACX) is one of the leading causes of deaths in Indian women. Chromosomal alterations including 11p15.5 locus were reported in CACX. Consequently, we strived for the first time to understand the molecular status of the candidate gene Insulin-like growth factor 2, IGF2 (11p15.5) in Indian CACX patients (n = 128). DNA copy number (CN) analysis using CGH-SNP analysis showed no genetic alteration and it was further validated by comparison with publicly available CN datasets. But promoter hypo-methylation during the progression of CACX was observed and also found to be concordant with publicly available DNA methylation datasets. Interestingly, we found diverse expression of IGF2 transcript in both normal cervical epithelium (NCE) and CACX tumors. Similar heterogeneous expression pattern was seen in publicly available expression datasets as well. Finally, protein expression analysis in NCE showed concordance with transcript expression but tumors showed frequent low expression. Log-rank test showed a difference (p-value = 0.057) in overall survival between cases with and without alteration for IGF2 in Indian CACX patients. Collectively, our study proposes that regulation of IGF2 expression in NCE appeared to be multifaceted and deregulation during the development of CACX resulted in the differential expression.

中文翻译：

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在印度宫颈癌的发展过程中，IGF2失控。

子宫宫颈癌（CACX）是印度女性死亡的主要原因之一。在CACX中报道了包括11p15.5基因座在内的染色体改变。因此，我们首次尝试了解印度CACX患者（n  = 128）中候选基因胰岛素样生长因子2，IGF2（11p15.5）的分子状态。使用CGH-SNP分析的DNA拷贝数（CN）分析未显示遗传改变，并且通过与可公开获得的CN数据集进行比较进行了进一步验证。但是，在CACX进展过程中观察到启动子低甲基化，并且发现其与公众可获得的DNA甲基化数据集一致。有趣的是，我们发现了IGF2的多种表达正常宫颈上皮（NCE）和CACX肿瘤中的转录本。在公开可用的表达数据集中也可以看到类似的异构表达模式。最后，NCE中的蛋白表达分析显示与转录表达一致，但肿瘤显示出频繁的低表达。对数秩检验表明，印度CACX患者中IGF2有无改变的总生存期之间存在差异（p值= 0.057）。总的来说，我们的研究表明，NCE中IGF2表达的调控似乎是多方面的，在CACX的发展过程中放松调控会导致差异表达。