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. 2022 Jul 5;29(7):4689-4702.
doi: 10.3390/curroncol29070372.

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

Alma D Campos-Parra  1 , Milagros Pérez-Quintanilla  2 , Antonio Daniel Martínez-Gutierrez  1 , Delia Pérez-Montiel  3 , Jaime Coronel-Martínez  2 , Oliver Millan-Catalan  1 , David Cantú De León  2 , Carlos Pérez-Plasencia  1   4
Affiliations

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

Alma D Campos-Parra et al. Curr Oncol. .

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.

Keywords: adenocarcinoma; cervical cancer; squamous cell carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular profile distinguishing cervical ADC and SCC in CC patients from the TCGA Database. Each column represents a patient with CC, and each row represents the expression of a gene. Gene expression changes are represented in blue (upregulated), red (downregulated), and white (no significant change or the absence of data). Patients with SCC are represented in green and ADCs in purple. There were 1768 unique DEGs between SCC and ADC tumors (adj p-value < 0.05, log2FoldChange >2 or <2), and most of the ADC tumors were clustered together.
Figure 2
Figure 2
Molecular profile distinguishing ADC and SCC in CC patients from the Mexican-Mestizo cohort. Each column represents a patient with CC, and each row represents the expression of a gene. Gene expression changes are represented in blue (upregulated), red (downregulated) and white (no significant change or the absence of data). Patients with SCC are represented in green and ADCs in purple. In total, 130 transcripts separated Mexican-Mestizo CC patients into ADC vs. SCC subgroups (adj p-value < 0.05).
Figure 3
Figure 3
DEGs in the Mexican-Mestizo CC dataset and the TCGA dataset are concordant. Blue represents the 88 unique DEGs in the Mexican-Mestizo CC dataset. Green represents the 70 DEGs from the TCGA dataset.
Figure 4
Figure 4
Signaling pathway enrichment analysis of DEGs between ADC and SCC patients performed with the WebGestalt platform. (A) Enriched pathways in the KEGG database analysis. (B) Enriched pathways in the WikiPathways database analysis. (C) Enriched pathways in the Reactome database analysis. The size of the dots represents the number of DEGs in the pathway, while the dot color represents the significance of the analysis, where red shows a more significantly enriched pathway.
Figure 5
Figure 5
Kaplan-Meier OS analysis of Mexican-Mestizo patients. (A) Differences in the OS of patients with high and low expression of GABRB2. (B) Differences in the OS of patients according to TSPAN8 expression. (C) Differences in the OS of patients according to TMEM40 expression. Blue lines represent patients with low gene expression, and red lines represent patients with high gene expression.
Figure 6
Figure 6
Kaplan-Meier OS analysis of independent Mexican cohort. (A) Differences in the OS of patients with high and low expression of GABRB2. (B) Differences in the OS of patients according to TSPAN8 expression. (C) Differences in the OS of patients according to TMEM40 expression. Blue lines represent patients with low gene expression, and red lines represent patients with high gene expression.
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