scholarly journals Molecular Differences Between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers

Author(s):  
Alma Campos-Parra ◽  
Milagros Perez-Quintanilla ◽  
Antonio Daniel Martínez-Gutierrez ◽  
Delia Pérez-Montiel ◽  
Oliver Millan-Catalan ◽  
...  

Abstract Purpose Cervical cancer (CC) remains a health problem. Persistent infection by high-risk papillomavirus (HR-HPV) is the main cause of this disease. The most frequently diagnosed histological types of CC are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. Our aim was to search for a molecular profile that distinguishes each histological subtype and predicts the prognosis of one or both subtypes would be of great benefit to these 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 between ADC and SCC. The differentially expressed genes obtained from the TCGA database were validated with an online, publicly available transcriptome dataset (GSE56303) containing data for a Mexican-Mestizo independent cohort. The global biological pathways involving differentially expressed genes between SSC and ADC were obtained by performing an analysis using the Webgestalt platform. In addition, associations of the differentially expressed genes with Overall Survival (OS) were assessed. Results The molecular profile of 70 altered transcripts between ADC and SCC patients from the TCGA cohort was determined. These transcripts were also deregulated in the Mexico-Mestizo cohort with the same Log2FoldChange values. The molecular pathways involved were IL-17, JAK/STAT and Ras signaling. Higher GABRB2 and TSPAN8 expression and lower TMEM40 expression were associated with better OS in the Mexican-Mestizo cohort. Conclusion We were able to detect molecular differences between the ADC and SCC subtypes of CC; however, further studies are required to define the appropriate prognostic biomarker for each histological type.

2020 ◽  
Vol 22 (1) ◽  
pp. 60
Author(s):  
Sichong Han ◽  
Zhe Wang ◽  
Jining Liu ◽  
Qipeng Yuan

Understanding the mechanism by which sulforaphene (SFE) affects esophageal squamous cell carcinoma (ESCC) contributes to the application of this isothiocyanate as a chemotherapeutic agent. Thus, we attempted to investigate SFE regulation of ESCC characteristics more deeply. We performed gene set enrichment analysis (GSEA) on microarray data of SFE-treated ESCC cells and found that differentially expressed genes are enriched in TNFα_Signaling_via_the_NFκB_Pathway. Coupled with the expression profile data from the GSE20347 and GSE75241 datasets, we narrowed the set to 8 genes, 4 of which (C-X-C motif chemokine ligand 10 (CXCL10), TNF alpha induced protein 3 (TNFAIP3), inhibin subunit beta A (INHBA), and plasminogen activator, urokinase (PLAU)) were verified as the targets of SFE. RNA-sequence (RNA-seq) data of 182 ESCC samples from The Cancer Genome Atlas (TCGA) were grouped into two phenotypes for GSEA according to the expression of CXCL10, TNFAIP3, INHBA, and PLAU. The enrichment results proved that they were all involved in the NFκB pathway. ChIP-seq analyses obtained from the Cistrome database indicated that NFκB-p65 is likely to control the transcription of CXCL10, TNFAIP3, INHBA, and PLAU, and considering TNFAIP3 and PLAU are the most significantly differentially expressed genes, we used chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to verify the regulation of p65 on their expression. The results demonstrated that SFE suppresses ESCC progression by down-regulating TNFAIP3 and PLAU expression in a p65-dependent manner.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
João Paulo Oliveira-Costa ◽  
Alex Fiorini Carvalho ◽  
Silvia Vanessa Lourenco ◽  
Luiz Paulo Kowalski ◽  
Dirce Maria Carraro ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Heyang Cui ◽  
Yongjia Weng ◽  
Ning Ding ◽  
Chen Cheng ◽  
Longlong Wang ◽  
...  

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors in China, and its prognosis remains poor. Autophagy is an evolutionarily conserved catabolic process involved in the occurrence and development of ESCC. In this study, we described the expression profile of autophagy-related genes (ARGs) in ESCC and developed a prognostic prediction model for ESCC patients based on the expression pattern of ARGs. We used four ESCC cohorts, GSE53624 (119 samples) set as the discovery cohort, The Cancer Genome Atlas (TCGA) ESCC set (95 samples) as the validation cohort, 155 ESCC cohort, and Oncomine cohort were used to screen and verify differentially expressed ARGs. We identified 34 differentially expressed genes out of 222 ARGs. In the discovery cohort, we divided ESCC patients into three groups that showed significant differences in prognosis. Then, we analyzed the prognosis of 34 differentially expressed ARGs. Three genes [poly (ADP-ribose) polymerase 1 (PARP1), integrin alpha-6 (ITGA6), and Fas-associated death domain (FADD)] were ultimately obtained through random forest feature selection and were constructed as an ARG-related prognostic model. This model was further validated in TCGA ESCC set. Cox regression analysis confirmed that the three-gene signature was an independent prognostic factor for ESCC patients. This signature effectively stratified patients in both discovery and validation cohorts by overall survival (P = 5.162E-8 and P = 0.052, respectively). We also constructed a clinical nomogram with a concordance index of 0.713 to predict the survival possibility of ESCC patients by integrating clinical characteristics and the ARG signature. The calibration curves substantiated fine concordance between nomogram prediction and actual observation. In conclusion, we constructed a new ARG-related prognostic model, which shows the potential to improve the ability of individualized prognosis prediction in ESCC.


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