Comprehensive transcriptome analysis identifies pathways with therapeutic potential in locally advanced cervical cancer.

Objective: The objective of the present study was to provide genomic and transcriptomic information that may improve clinical outcomes for locally advanced cervical cancer (LACC) patients by searching for therapeutic targets or potential biomarkers through the analysis of significantly altered signaling pathways in LACC.

Methods: Microarray-based transcriptome profiling of 89 tumor samples from women with LACC was performed. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, significantly over-expressed genes in LACC were identified; these genes were validated by quantitative reverse transcription-polymerase chain reaction in an independent cohort, and the protein expression data were obtained from the Human Protein Atlas.

Results: A transcriptome analysis revealed 7530 significantly over-expressed genes in LACC samples. By KEGG analysis, we found 93 dysregulated signaling pathways, including the JAK-STAT, NOTCH and mTOR-autophagy pathways, which were significantly upregulated. We confirmed the overexpression of the relevant genes of each pathway, such as NOTCH1, JAK2, STAM1, SOS1, ADAM17, PSEN1, NCSTN, RPS6, STK11/LKB1 and MLTS8/GBL in LACC compared with normal cervical tissue epithelia.

Conclusions: Through comprehensive genomic and transcriptomic analyses, this work provides information regarding signaling pathways with promising therapeutic targets, suggesting novel target therapies to be considered in future clinical trials for LACC patients.