Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses. MiRNA expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery using Agilent human miRNA microarrays based on miRBase (release 18.0) GeneChip®.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patientsM-bM-^@M-^Y survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify mRNA markers for ESCC CRT-response prediction through gene expression analyses. Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery and 10 normal esophageal epithelia using Affymetrix U133 Plus 2.0 arrays.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses.
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma. Total RNA obtained from peripheral whole blood before and after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. 21 patients with 42 samples were analyzed. The expression profiles from pathological complete responders were compared to non-complete responders.
Project description:Neoadjuvant therapy has been shown to improve survival for locally advanced esophageal squamous cell carcinoma (ESCC). However, some cases may acquire therapy resistance and the mechanism is still unclear. Here, we applied single-cell RNA sequencing on 7 ESCC patients with neoadjuvant therapy and 2 ESCC patients underwent general surgery alone to delineate the tumor heterogeneity, tumor microenvironment (TME) and potential hallmarks of therapy resistance. In total, 13 tumor cell lineages and its corresponding lineage-specific gene signatures, pathway activities, and transcription factors were identified, representing different mechanisms and hallmarks of neoadjuvant therapy resistance, such as oxidative stress response, hypoxia, DNA repair, ECM and EMT. Typically, tumor cell lineage Ep-C2 with signatures of oxidative stress response showed the strongest resistance to neoadjuvant therapy, particularly under chemoradiotherapy and immunotherapy combination. Excepting for the resistance mechanisms associated with tumor cell lineages, we also investigated three TME characteristics response to neoadjuvant therapy resistance, including the infiltration of cytotoxic-insufficient GZMK+ effector memory T cells, angiogenesis-promoting effect of myeloid lineages and the cell-cell communication of tumor-associated fibroblasts. These hallmarks of neoadjuvant therapy will help us to understand the therapy resistance in ESCC and provide important clues to identify potential targets to improve therapy sensitivity.
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma.
Project description:Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors. In the current study we focus on biallelic loss and its relation to expression of mRNA and miRNA in ESCC using results from 500K SNP, mRNA, and miRNA arrays in 30 cases from a high-risk region of China.
Project description:Esophageal squamous cell carcinoma (ESCC) accounts for ~90% of all cases of esophageal cancer and the sixth most common cause of cancer related death worldwide. 1, 2 It remains a globally challenging disease and mostly diagnosed cases requires a multidisciplinary approach with extensive treatments including surgery, chemoradiotherapy and/or chemotherapy. ESCC has a relatively high tumor mutational burden,3 suggesting that it could benefit from PD-1 blockade. Recently, three phase III clinical trials reported that PD-1 blockade significantly improved progression-free survival (PFS) and overall survival (OS) when combined with chemotherapy as first-line therapy in advanced/metastatic ESCC.4, 5 Moreover, in 2021 ASCO annual meeting, two phase II clinical trials reported that neoadjuvant chemo-immunotherapy (NACI) induced an obvious improvement of the pathologic complete response (pCR) for resectable ESCC (35. 3% and 42.5%, respectively). Several phase III trials on this topic are ongoing (NCT04807673, NCT04848753, NCT04280822) (https://clinicaltrial s.gov/ct2/show/NCT04807673), indicating that neoadjuvant NACI would become promising treatment for locally advanced ESCC. Nevertheless, not all ESCC patients could respond to NACI. Patients who responded well or poorly to neoadjuvant immunotherapy were treated with surgery. We collected samples from these patients and conducted single-cell sequencing to analyze the tumor immune microenvironment of patients with different therapeutic effects, compare the differences in immune cell composition in the immune microenvironment, and explore more effective neoadjuvant therapy methods.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify mRNA markers for ESCC CRT-response prediction through gene expression analyses.
