Molecular Differences between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers

Abstract

The most frequently diagnosed histological types of cervical cancer (CC) are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. A molecular profile that distinguishes each histological subtype and predicts the prognosis would be of great benefit to CC patients. Methods: The transcriptome of CC patients from The Cancer Genome Atlas (TCGA) was analyzed using the DESeq2 package to obtain the differentially expressed genes (DEGs) between ADC and SCC. The DEGs were validated on a publicly available Mexican-Mestizo patient transcriptome dataset (GSE56303). The global biological pathways involving the DEGs were obtained using the Webgestalt platform. The associations of the DEGs with Overall Survival (OS) were assessed. Finally, three DEGs were validated by RT-qPCR in an independent cohort of Mexican patients. Results. The molecular profiles of ADC and SCC of the CC patients of the TCGA database and the Mexican-Mestizo cohort (GSE56303) were determined obtaining 1768 and 88 DEGs, respectively. Strikingly, 70 genes were concordant—with similar Log2FoldChange values—in both cohorts. The 70 DEGs were involved in IL-17, JAK/STAT, and Ras signaling. Kaplan-Meier OS analysis from the Mexican-Mestizo cohort showed that higher GABRB2 and TSPAN8 and lower TMEM40 expression were associated with better OS. Similar results were found in an independent Mexican cohort. Conclusions: Molecular differences were detected between the ADC and SCC subtypes; however, further studies are required to define the appropriate prognostic biomarker for each histological type.

Bioinformatics analysis of immune characteristics in tumors with alternative carcinogenesis pathways induced by human papillomaviruses

“…1 A). Cluster 3 of CC samples was predominantly composed of nonsquamous cell neoplasms (adenocarcinomas), reflecting the distinctness of global expression profiles of cervical adenocarcinomas [ 25 ]. The division of squamous cell CC samples into two clusters also reflected the clustering of their global expression profiles [ 26 ].…”

RIPOR2 Expression Decreased by HPV-16 E6 and E7 Oncoproteins: An Opportunity in the Search for Prognostic Biomarkers in Cervical Cancer

“…Although little information is available about those cellular elements deregulated by viral oncoproteins that could be used as biomarkers associated with clinical outcome in CC. The study of molecules based on RNAs, identified by massive RNA sequencing, provides extensive information on those molecules altered in cervical cancer [ 16 ], in addition to those altered by viral oncogenes that could eventually serve as prognostic biomarkers, as is proposed in this study. With this in mind, we analyzed the transcriptome of cervical cancer C-33 A cells stably transfected with HPV E6 or E7 oncogenes, to further identify potential prognostic biomarkers in CC.…”

“…In this regard, some proteins have been proposed as prognostic biomarkers for CC, including the increased of Ki-67/MIB-1 protein levels [ 11 ], glucose-6-phosphatase catalytic subunit (G6PC) [ 12 ], and serine/arginine-rich protein-specific kinase 1 (SRPK1) [ 13 ], which are related with worse survival, while the high levels of Galectin 9 [ 14 ] correlate with a better prognosis in CC patients. Moreover, through the analysis of transcriptional profiles derived from genomic databases of CC patients, genes related to OS have been identified [ 15 , 16 ]. For instance, the high expression of BRCA1 [ 17 ] is associated with better OS, while high levels of VEGF165 transcript have been associated with worse disease-free survival [ 18 ] in CC patients.…”

NAD+ Metabolism-Related Gene Profile Can Be a Relevant Source of Squamous Cell Carcinoma Biomarkers

“…CeSCC is the most common gynecological tumor and the fourth leading cause of cancer-related death in women. The primary risk factor for CeSCC is persistent infections with alpha-type HPVs [3,4].…”