GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity
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Williams Fernandes Barra1,*, Fabiano Cordeiro Moreira1,*, Aline Maria Pereira Cruz1, André Salim Khayat1, Danielle Queiroz Calcagno1, Ney Pereira Carneiro dos Santos1, Rui Wanderley Mascarenhas Junior1, Taíssa Maíra Thomaz Araújo1, Geraldo Ishak1,2, Samia Demachki1, Rommel Mario Rodríguez Burbano1, Ândrea Kely Campos Ribeiro dos Santos1, Sidney Emanuel Batista dos Santos1, Gregory Joseph Riggins3 and Paulo Pimentel de Assumpção1
1Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Brazil
2Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Brazil
3Brain Cancer Biology and Therapy Research Laboratory, Johns Hopkins Medicine, Baltimore, MD, USA
Paulo Pimentel de Assumpção, email: [email protected]
Keywords: gastroesophageal junction; 7th UICC; TCGA; molecular fingerprints; expression pattern
Received: August 24, 2017 Accepted: September 21, 2017 Published: October 31, 2017
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 Log2 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) |Log2 (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.
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