TY - JOUR
T1 - GEJ cancers
T2 - Gastric or esophageal tumors? Searching for the answer according to molecular identity
AU - Barra, Williams Fernandes
AU - Moreira, Fabiano Cordeiro
AU - Cruz, Aline Maria Pereira
AU - Khayat, André Salim
AU - Calcagno, Danielle Queiroz
AU - dos Santos, Ney Pereira Carneiro
AU - Junior, Rui Wanderley Mascarenhas
AU - Araújo, Taíssa Maíra Thomaz
AU - Ishak, Geraldo
AU - Demachki, Samia
AU - Burbano, Rommel Mario Rodríguez
AU - dos Santos, ândrea Kely Campos Ribeiro
AU - dos Santos, Sidney Emanuel Batista
AU - Riggins, Gregory Joseph
AU - de Assumpção, Paulo Pimentel
N1 - Funding Information:
We acknowledge PROPESP/Universidade Federal do Pará for financial support and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for fellowship support. CAPES (Coordenação de Aperfeiçoamento de Pessoal do Nível Superior) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) were the funding sources of this study that helped in purchasing equipaments.
Publisher Copyright:
© Barra et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - 7 UICC
KW - Expression pattern
KW - Gastroesophageal junction
KW - Molecular fingerprints
KW - TCGA
UR - http://www.scopus.com/inward/record.url?scp=85035351318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85035351318&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.22216
DO - 10.18632/oncotarget.22216
M3 - Article
C2 - 29262640
AN - SCOPUS:85035351318
SN - 1949-2553
VL - 8
SP - 104286
EP - 104294
JO - Oncotarget
JF - Oncotarget
IS - 61
ER -