Gene expression profiles of esophageal squamous cell cancers in Hodgkin lymphoma survivors versus sporadic cases

Abstract

Hodgkin lymphoma (HL) survivors are at increased risk of developing second primary esophageal squamous cell cancer (ESCC). We aimed to gain insight in the driving events of ESCC in HL survivors (hESCC) by using RNA sequencing and NanoString profiling. Objectives were to investigate differences in RNA signaling between hESCC and sporadic ESCC (sESCC), and to look for early malignant changes in non-neoplastic esophageal tissue of HL survivors (hNN-tissue). We analyzed material of 26 hESCC cases, identified via the Dutch pathology registry (PALGA) and 17 sESCC cases from one academic institute and RNA sequencing data of 44 sESCC cases from TCGA. Gene expression profiles for the NanoString panel PanCancer IO 360 were obtained from 16/26 hESCC and four hNN-tissue, while non-neoplastic squamous tissue of four sporadic cases (sNN-tissue) served as reference profile. Hierarchical clustering, differential expression and pathway analyses were performed. Overall, the molecular profiles of hESCC and sESCC were similar. There was increased immune, HMGB1 and ILK signaling compared to sNN-tissue. The profiles of hNN-tissue were distinct from sNN-tissue, indicating early field effects in the esophagus of HL survivors. The BRCA1 pathway was upregulated in hESCC tissue, compared to hNN tissue. Analysis of expression profiles reveals overlap between hESCC and sESCC, and differences between hESCC and its surrounding hNN-tissue. Further research is required to validate our results and to investigate whether the changes observed in hNN-tissue are already detectable before development of hESCC. In the future, our findings could be used to improve hESCC patient management.

Gene Expression in Barrett’s Esophagus Cell Lines Resemble Esophageal Squamous Cell Carcinoma Instead of Esophageal Adenocarcinoma

“…To validate these gene expression signatures, we tested ESCC cases ( n = 23) from GSE130078 [ 39 ] ( Figure 1 B) and EAC cases from E-MTAB-4054 ( n = 17) [ 43 ] ( Figure 1 C), GSE37200 ( n = 15) [ 32 , 33 , 34 , 35 ] ( Figure 1 D), GSE112926 ( n = 51) [ 38 ] ( Figure 1 E), and GSE165252 ( n = 77) [ 40 ] ( Figure 1 F). Except for a few outliers, which may have been previously misclassified, the ESCC and EAC cases from these datasets clustered with corresponding cases from TCGA ( Figure 1 B–F), thereby validating the signatures of EAC and ESCC.…”

“…For the Genotype-Tissue Expression (GTEx) dataset [ 29 ], gene expression data (v8) were obtained from (accessed on 17 June 2021). Gene expression data of 13 datasets were obtained from Gene Expression Omnibus ( ) (accessed on 17 June 2021): GSE2144 [ 30 ], GSE9768, GSE13376 [ 31 ], GSE13378 [ 31 ], GSE37200 [ 32 , 33 , 34 , 35 ], GSE57130 [ 36 ], GSE58963, GSE62909 [ 37 ], GSE112926 [ 38 ], GSE130078 [ 39 ], GSE165252 [ 40 ], GSE173166 [ 41 ], and GSE173169 [ 41 ]. Gene expression data of 3 datasets were obtained from Expression Atlas: E-MTAB-2706 [ 42 ] ( ) (accessed on 17 June 2021), E-MTAB-3983 ( ) (accessed on 17 June 2021), and E-MTAB-4054 [ 43 ] ( ) (accessed on 17 June 2021).…”

“…Gene expression data of 13 datasets were obtained from Gene Expression Omnibus (https://www.ncbi.nlm. nih.gov/geo/query/acc.cgi?acc=) (accessed on 17 June 2021): GSE2144 [30], GSE9768, GSE13376 [31], GSE13378 [31], GSE37200 [32][33][34][35], GSE57130 [36], GSE58963, GSE62909 [37], GSE112926 [38], GSE130078 [39], GSE165252 [40], GSE173166 [41], and GSE173169 [41]. Gene expression data of 3 datasets were obtained from Expression Atlas: E-MTAB-2706 [42] (https://www.ebi.ac.uk/gxa/experiments/E-MTAB-2706/Downloads) (accessed on 17 June 2021), E-MTAB-3983 (https://www.ebi.ac.uk/gxa/experiments/E-MTAB-3983/ Downloads) (accessed on 17 June 2021), and E-MTAB-4054 [43] (https://www.ebi.ac.…”