Comparative Molecular Analyses of Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, and Gastric Adenocarcinoma

Abstract

This study highlights the genomic heterogeneity of gastroesophageal cancers, showing striking molecular differences between tumors originating from different locations. Moreover, this study showed that esophageal squamous cell carcinomas exhibit a unique molecular profile, whereas gastric adenocarcinomas and esophageal adenocarcinomas have some similarities, supporting the fact that adenocarcinomas and squamous cell carcinomas are completely different diseases, irrespective of the tumor location. This raises the question of whether treatment of gastroesophageal tumors should be determined according to histological subtype and molecular targets rather than anatomical site. These findings provide insights that could enable physicians to better select patients and inform therapeutic choices in order to improve clinical outcome.

ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach

“…The literature search identified globally 158 unduplicated articles, 126 of which were excluded after reviewing their title/abstract, which left 32 articles eligible for full text review. After applying our inclusion and exclusion criteria, 18 articles (for 17 cohorts) were selected for this systematic review [7,[59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75] (supplementary Figure S1, available at Annals of Oncology online).…”

“…The vast majority of the cohorts reported data on patients from the USA, followed by Asian and European subjects. The majority of the manuscripts (59%) investigated original cohorts of patients [7,61,[63][64][65][66][67][68][69][70]75], whereas data derived from external (public or private) databases were used in some papers [59,62,[71][72][73][74].…”

“…TMB was assessed using whole-exome sequencing in 5 (29%) studies [7,59,60,69,70], and using multigene cancer panels in the remaining 12 (71%), where TMB-high is variably defined as tumours showing at least 17 or 20 mutations/Mb upon sequencing of at least 1.2-1.5 Mb [61][62][63][64][65][66][67][71][72][73][74][75]. To assess MSI status, an approach based on both IHC to assess MMR status and/or molecular assessment of microsatellites by MSI-PCR and NGS was applied in most studies (82%) [7, 59-61, 64, 66, 68-75].…”

Rap1A promotes esophageal squamous cell carcinoma metastasis through the AKT signaling pathway

“…In summary, the present study demonstrated that Rap1A promoted tumor metastasis, possibly via AKT signaling, integrin-mediated adhesion (27,36), MMP9 and EMT; furthermore, the growth-promoting effects of Rap1A in ESCC were associated with tumor heterogeneity, which required further research to elucidate the underlying mechanism. Considering the known amplification of the K-Ras gene in human esophageal cancer (31,32,37), the expression of Rap1A may be an ESCC marker, and inhibitors of Rap1A may be of therapeutic value. In addition, mTOR plays a key role in regulating several fundamental cellular processes, and its hyperactivation is correlated with a number of human cancers (38).…”

Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer

“…Investigation into their mechanisms will be helpful in preventing and detecting the disease earlier, with the potential to develop new therapeutic targets. 7 …”