Aim

We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection.

Materials and methods

Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.

Results

We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated.

Conclusion

Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.

中文翻译：

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HPV相关宫颈癌发生过程中的转录组比较分析：II类MHC和免疫球蛋白重链基因的意义。

目标

我们旨在确定与高危人类乳头瘤病毒（HPV）感染相关的宫颈癌发生的生物学过程和途径。

材料和方法

从三个福尔马林固定石蜡包埋（FFPE）样品中提取总RNA，每个样品分别为正常宫颈，HPV感染的低度鳞状上皮内病变（LSIL），高度SIL（HSIL）和鳞状细胞癌（SCC）。通过微阵列进行转录组分析，然后进行下游基因本体论（GO）和《京都基因与基因组百科全书》（KEGG）途径富集分析。

结果

我们检查了从正常子宫颈到LSIL，HSIL和SCC的每个过渡阶段富集的GO的差异，发现了307个基因被差异表达。在从正常子宫颈到LSIL的过渡过程中，细胞外基质（ECM）基因被显着下调。从LSIL到HSIL的过渡过程中，MHC II类基因显着上调。在从HSIL到SCC的最后过渡中，免疫球蛋白重基因座基因被显着上调，并且牵涉到ECM途径。

结论

包括MHC II和免疫球蛋白重链基因在内的免疫相关基因的失调参与了从LSIL到HSIL和SCC的转变，表明免疫逃避了宿主的抗肿瘤反应。在宫颈癌发生的早期和晚期，细胞外基质起着重要作用。