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Background: Patients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ ACs) face poor outcomes. Thus sensitive biomarkers for improved clinical management are highly warranted. Detection of circulating tumor DNA (ctDNA) using DNA methylation biomarkers is a highly sensitive approach for cancer detection and management. Here, we explored the potential of a tumor-agnostic test targeting DNA methylation to detect ctDNA in patients with resectable and advanced G-GEJ ACs. Material and methods: A tumor-agnostic digital PCR test—TriMeth—targeting the gastrointestinal cancer-specific methylated genes C9orf50, KCNQ5, and CLIP4 was carried out on a total of 131 study patients. DNA from surgical tumor specimens of 29 patients with G-GEJ ACs and plasma cell-free DNA from 52 patients with advanced and resectable G-GEJ ACs, and from 50 healthy controls, were analyzed. Results: Methylated tumor DNA was detected by TriMeth in all of the surgical tumor specimens (29/29, 100%). Furthermore, TriMeth detected ctDNA in plasma from 31/52 (60%) patients with G-GEJ AC, including in 13/17 (76%) advanced cases, and 18/35 (51%) resectable cases. ctDNA was not detected in healthy controls (0/50, 0%). Conclusions: This study demonstrates that TriMeth may hold potential as a biomarker for identifying ctDNA in patients with G-GEJ ACs. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.

Esophageal and gastroesophageal junction (GEJ) malignancies are aggressive, and survival is poor once metastasis occurs. The most common sites of metastatic involvement include the liver, lymph nodes, lung, peritoneum, adrenal glands, bone, and brain, while skeletal muscle (SM) involvement is rare. We report a case of a 68-year-old female who presented with intractable emesis for one month and was found to have a primary GEJ adenocarcinoma measuring up to 6.7 cm. Endoscopic biopsy revealed poorly differentiated GEJ adenocarcinoma with positive AE1/AE3 immunostains. Positron emission tomography/computed tomography and magnetic resonance imaging revealed metastases to the omentum and left lower extremity SMs, including the proximal adductor longus, adductor magnus, and gluteus minimus. This study reviews the literature on SM metastasis in esophageal and GEJ cancer, GEJ cancer classification, incidence, treatment, and prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sabu et al.)

Aim: The purpose of this study was to assess the role of marital status in esophageal adenocarcinoma (EAC). Methods: We identified 8341 EAC patients based on the Surveillance, Epidemiology and End Results database during 2007-2015, of whom 7275 were male and 1066 were female. Temporal trends, competing risk analysis and propensity score matching were performed. Results: There was an upward trend for the rate of unmarried patients in both male and female populations (p < 0.05). Unmarried status represented an independent risk factor for higher cancer-specific death (CSD) in males (hazard ratio: 1.11; 95% CI: 1.04-1.18; p = 0.001) but not in females (hazard ratio: 0.96; 95% CI: 0.81-1.13; p = 0.610). Married EAC patients experienced lower CSD compared with their unmarried counterparts in the male cohort. [ABSTRACT FROM AUTHOR]

Background The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. Here, we aimed at developing a miRNA-based signature for predicting the prognosis of esophagus adenocarcinoma (EAC). Methods The RNA-sequencing data set of EAC was downloaded from The Cancer Genome Atlas (TCGA). Eighty-four patients with EAC were classified into a training set and a test set randomly. Using univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), we identified prognostic factors and constructed a prognostic miRNA signature. The accuracy of the signature was evaluated by the receiver operating characteristic (ROC) curve. Result In general, in the training set, six miRNAs (hsa-mir-425, hsa-let-7b, hsa-mir-23a, hsa-mir-3074, hsa-mir-424 and hsa-mir-505) displayed good prognostic power as markers of overall survival for EAC patients. Relative to patients in the low-risk group, those assigned to the high-risk group according to their risk scores of the designed miRNA model displayed reduced overall survival. This 6-miRNA model was validated in test and entire set. The area under curve (AUC) for ROC at 3 years was 0.959, 0.840, and 0.868 in training, test, and entire set, respectively. Molecular functional analysis and pathway enrichment analysis indicated that the target messenger RNAs associated with 6-miRNA signature were closely related to several pathways involved in carcinogenesis, especially cell cycle. Conclusion In summary, a novel 6-miRNA expression-based prognostic signature derived from the EAC data of TCGA was constructed and validated for predicting the prognosis of EAC.

Background Understanding the molecular mechanisms represents an important step in the development of diagnostic and therapeutic measures of esophagus adenocarcinoma (NOS). The objective of this study is to identify the epigenetic regulation on gene expression in NOS, shedding light on the molecular mechanisms of NOS. Methods In this study, 78 patients with NOS were included and the data of mRNA, miRNA and DNA methylation of were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis between NOS and controls was performed in terms of gene expression, miRNA expression, and DNA methylation. Bioinformatic analysis was followed to explore the regulation mechanisms of miRNA and DNA methylationon gene expression. Results Totally, up to 1320 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs were identified. 240 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. 101 DEGs were found to be highlymethylated in CpG islands. Then, 8 differentially methylated genes (DMGs) were selected, which showed down-regulated expression in NOS. Among of these genes, 6 genes including ADHFE1, DPP6, GRIA4, CNKSR2, RPS6KA6 and ZNF135 were target genes of differentially expressed miRNAs (hsa-mir-335, hsa-mir-18a, hsa-mir-93, hsa-mir-106b and hsa-mir-21). Conclusions The identified altered miRNA, genes and DNA methylation site may be applied as biomarkers for diagnosis and prognosis of NOS. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted. [ABSTRACT FROM AUTHOR]

Summary Alterations of the epidermal growth factor receptor (EGFR) can be observed in a significant subset of esophageal adenocarcinomas (EACs), and targeted therapy against EGFR may become an interesting approach for the treatment of these tumors. Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the responsiveness against anti-EGFR therapy in colorectal carcinomas. We investigated the prevalence of these events in a collection of 117 primary resected EACs, correlated the findings with EGFR expression and amplification, and determined their clinicopathologic impact. KRAS mutations were detected in 4 (3%) of 117 tumors (3x G12D and 1 G12V mutation). One tumor had a PIK3CA E545K mutation. Neither NRAS nor BRAF mutations were detected. Sixteen (14%) of 117 cases were negative for PTEN expression, determined by immunohistochemistry. Loss of PTEN was observed predominantly in advanced tumor stages (P = .004). There was no association between PTEN and EGFR status. Loss of PTEN was associated with shorter overall and disease-free survival (P < .001 each) and also an independent prognostic factor in multivariate analysis (P = .015). EGFR status had no prognostic impact in this case collection. In summary, loss of PTEN can be detected in a significant subset of EAC and is associated with an aggressive phenotype. Therefore, PTEN may be useful as a prognostic biomarker. In contrast, mutations of RAS/RAF/PIK3CA appear only very rarely, if at all, in EAC. A possible predictive role of PTEN in anti-EGFR treatment warrants further investigations, whereas determination of RAS/RAF/PIK3CA mutations may only have a minor impact in this context. [ABSTRACT FROM AUTHOR]

Introduction Lymph node involvement is the most important predictor of prognosis in oesophageal cancer. The present study describes our single-centre experience of lymphadenopathy in oesophageal carcinoma cases at a tertiary care centre in the Marathwada region of Maharashtra state in western India. Methods This descriptive study included 31 patients who were operated for oesophageal carcinoma at the State Cancer Hospital in Marathwada from August 2015 to September 2017. Thirty patients underwent three-field lymph node dissections, and one patient underwent Ivor Lewis surgery with two-field lymph node dissections. Three-field lymph node dissections were through a thoracotomy, followed by laparotomy and left cervical incision. The lymphatic metastases were categorised as (a) adjacent node metastases, (b) multiple levels of lymph node metastases, and (c) skip node metastases. The histopathological assessment of the removed specimen and lymph nodes was done. Pathologists evaluated the character and depth of the primary tumour and its invasion and node involvement. The location and numbers of positive and negative nodes were recorded. Results A total of 31 patients were included in the study, of which 17 had lymph node involvement. A total of 946 lymph nodes were dissected and examined, and the average number of lymph nodes removed per patient was 30.51. Among the 28 squamous cell carcinoma cases, lymph node involvement was found in 14 cases (50%) whereas, in adenocarcinoma, all the three cases showed lymph node involvement. In 11 cases of squamous cell carcinoma, thoracic lymph nodes were involved, whereas abdominal lymph nodes were involved in nine and cervical lymph nodes in two cases. Thoracic lymph nodes were involved in two cases of adenocarcinoma and abdominal lymph nodes were involved in one case of adenocarcinoma. Conclusions Squamous cell carcinoma was the predominant type, and lymph node metastasis was observed in 50% of these cases. Thoracic lymph nodes were more commonly involved. Tumour staging T2 and T3 had an increasing percentage of lymph nodes involved. Lymph node involvement was more in moderately differentiated and undifferentiated oesophageal cancers., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Boralkar et al.)

Background: The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. Here, we aimed at developing a miRNA-based signature for predicting the prognosis of esophagus adenocarcinoma (EAC)., Methods: The RNA-sequencing data set of EAC was downloaded from The Cancer Genome Atlas (TCGA). Eighty-four patients with EAC were classified into a training set and a test set randomly. Using univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), we identified prognostic factors and constructed a prognostic miRNA signature. The accuracy of the signature was evaluated by the receiver operating characteristic (ROC) curve., Result: In general, in the training set, six miRNAs (hsa-mir-425, hsa-let-7b, hsa-mir-23a, hsa-mir-3074, hsa-mir-424 and hsa-mir-505) displayed good prognostic power as markers of overall survival for EAC patients. Relative to patients in the low-risk group, those assigned to the high-risk group according to their risk scores of the designed miRNA model displayed reduced overall survival. This 6-miRNA model was validated in test and entire set. The area under curve (AUC) for ROC at 3 years was 0.959, 0.840, and 0.868 in training, test, and entire set, respectively. Molecular functional analysis and pathway enrichment analysis indicated that the target messenger RNAs associated with 6-miRNA signature were closely related to several pathways involved in carcinogenesis, especially cell cycle., Conclusion: In summary, a novel 6-miRNA expression-based prognostic signature derived from the EAC data of TCGA was constructed and validated for predicting the prognosis of EAC., Competing Interests: The authors declare that they have no competing interests.