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. 2017 Oct 31;8(61):104286-104294.
doi: 10.18632/oncotarget.22216. eCollection 2017 Nov 28.

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

Williams Fernandes Barra  1 , Fabiano Cordeiro Moreira  1 , Aline Maria Pereira Cruz  1 , André Salim Khayat  1 , Danielle Queiroz Calcagno  1 , Ney Pereira Carneiro Dos Santos  1 , Rui Wanderley Mascarenhas Junior  1 , Taíssa Maíra Thomaz Araújo  1 , Geraldo Ishak  1   2 , Samia Demachki  1 , Rommel Mario Rodríguez Burbano  1 , Ândrea Kely Campos Ribeiro Dos Santos  1 , Sidney Emanuel Batista Dos Santos  1 , Gregory Joseph Riggins  3 , Paulo Pimentel de Assumpção  1
Affiliations

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

Williams Fernandes Barra et al. Oncotarget. .

Abstract

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.

Keywords: 7th UICC; TCGA; expression pattern; gastroesophageal junction; molecular fingerprints.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
(A) PCA of 20,349 mRNAs and 910 microRNAs; (B) Heat Map of 2,366 mRNAs and 61 microRNAs differentially expressed (p-value < 0.05; |Log2(fold-change)| > 2) comparing non-cardia gastric adenocarcinomas, cardia adenocarcinomas and esophageal adenocarcinomas with esophageal squamous cell carcinomas.
Figure 2
Figure 2
(A) PCA of 20,349 mRNAs and 910 microRNAs; (B) Heat Map of 2550 mRNAs and 60 microRNAs differentially expressed (p-value < 0.05; |Log2(fold-change)| > 2) comparing esophageal adenocarcinomas and esophageal squamous cell carcinomas.
Figure 3
Figure 3. PCA of 20,349 mRNAs and 910 microRNAs
In (A) comparison between esophagus adenocarcinomas and non-cardia gastric adenocarcinomas; in (B) comparison between lower esophagus, gastric cardia region and non-cardia gastric adenocarcinomas.
Figure 4
Figure 4. PCA of 20,349 mRNAs and 910 microRNAs from gastric cancer, esophageal squamous cell carcinoma and colon adenocarcinoma samples
See this image and copyright information in PMC

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