Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis

Abstract

Cervical cancer is one of the most malignant reproductive diseases seen in women worldwide. The identification of dysregulated genes in clinical samples of cervical cancer may pave the way for development of better prognostic markers and therapeutic targets. To identify the dysregulated genes (DEGs), we have retrospectively collected 10 biopsies, seven from cervical cancer patients and three from normal subjects who underwent a hysterectomy. Total RNA isolated from biopsies was subjected to microarray analysis using the human Clariom D Affymetrix platform. Based on the results of principal component analysis (PCA), only eight samples are qualified for further studies; GO and KEGG were used to identify the key genes and were compared with TCGA and GEO datasets. Identified genes were further validated by quantitative real-time PCR and receiver operating characteristic (ROC) curves, and the highest Youden index was calculated in order to evaluate cutoff points (COPs) that allowed distinguishing of tissue samples of cervical squamous carcinoma patients from those of healthy individuals. By comparative microarray analysis, a total of 108 genes common across the six patients’ samples were chosen; among these, 78 genes were upregulated and 26 genes were downregulated. The key genes identified were SPP1, LYN, ARRB2, COL6A3, FOXM1, CCL21, TTK, and MELK. Based on their relative expression, the genes were ordered as follows: TTK > ARRB2 > SPP1 > FOXM1 > LYN > MELK > CCL21 > COL6A3; this generated data is in sync with the TCGA datasets, except for ARRB2. Protein-protein interaction network analysis revealed that TTK and MELK are closely associated with SMC4, AURKA, PLK4, and KIF18A. The candidate genes SPP1, FOXM1, LYN, COL6A3, CCL21, TTK and MELK at mRNA level, emerge as promising candidate markers for cervical cancer prognosis and also emerge as potential therapeutic drug targets.

FOXM1 Contributes to Chemotherapy Sensitivity in Cervical Cancer by Regulating TTK

“…In this study, we confirmed that FOXM1 and TTK showed high expression levels in the cervical cancer tissues, which were consistent with many studies [23][24][25]. FOXM1 and TTK play important roles in cell cycle progression.…”

Data mining for predictive analysis in gynecology: a focus on cervical health

“…On the other hand, new platforms like the BGISEQ-500 connected to the classification of the database are used in quercetin-based pharmaceutical antitumor treatments for uterine cancer to produce results on the genes that are differentially expressed [26]. Certain medical diagnoses related to the illness have been applied in some cases with an emphasis on crucial information extraction algorithms [27]. The value added is the knowledge that physicians contribute that may have a significant impact on the advancement of medicine by bringing awareness to information technology.…”

Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis

“…Initiation and development of CC is a complex process [8]. Although HPV infection is the critical determinant for the risk of developing CC, not all women infected with HPV develop CC.…”

“…Persistent infections with 14 high-risk HPV genotypes are responsible for nearly all occurrences of cervical squamous cell carcinoma (CSCC) and adenocarcinoma [28]. Women infected with HPV develop precancerous phases with low-grade squamous intraepithelial lesions/CIN I (LSIL) and high-grade intraepithelial lesions or CIN II/CIN III (HSIL), and these high-grade lesions eventually lead to invasive CC over a period of time [6][7][8]. The role of HPV infection in tumor initiation and progression has been elegantly reviewed by Deligeoroglou et al [29] and Steinbach and Riemer [30], and reports have been published on the mechanisms of immortalization of the host cells by HPV through signaling pathway dysregulation [11,[31][32][33], genomic instability [34,35], alteration of the microbiome [36][37][38][39], and immune response modulation [40][41][42][43][44].…”