GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.

Autor: Barra WF; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Moreira FC; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Pereira Cruz AM; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Khayat AS; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Calcagno DQ; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Carneiro Dos Santos NP; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Mascarenhas Junior RW; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Thomaz Araújo TM; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Ishak G; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil.; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Brazil., Demachki S; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Rodríguez Burbano RM; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Campos Ribeiro Dos Santos ÂK; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Batista Dos Santos SE; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil., Riggins GJ; Brain Cancer Biology and Therapy Research Laboratory, Johns Hopkins Medicine, Baltimore, MD, USA., Pimentel de Assumpção P; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil.
Jazyk: angličtina
Zdroj: Oncotarget [Oncotarget] 2017 Oct 31; Vol. 8 (61), pp. 104286-104294. Date of Electronic Publication: 2017 Oct 31 (Print Publication: 2017).
DOI: 10.18632/oncotarget.22216
Abstrakt: The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log 2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log 2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.
Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.
Databáze: MEDLINE