Objective:To determine whether prognostic nutritional index (PNI) affects clinical outcome through local immunity in esophageal cancers.Background:PNI is an indicator of nutritional status and systemic immune competence, and has attracted attention as a prognostic biomarker. Tumor-infiltrating lymph

Prognostic Nutritional Index, Tumor-infiltrating Lymphocytes, and Prognosis in Patients with Esophageal Cancer

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients’ survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC. Esophageal squamous-cell carcinomas (ESCC) have poor prognosis, and detailed molecular profiles are necessary to identify prognostic markers. Here the authors analyse 60 ESCC patient samples using scRNA-seq, TCR-seq and genomics; they find mucosal immunity markers associated with survival and immunosuppressive microenvironments.

/pdf/dissecting-esophageal-squamous-cell-carcinoma-ecosystem-by-p4hha7z28l.pdf

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis.

Abstract Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m 7 G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m 7 G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m 7 G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m 7 G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment. 

/pdf/n7-methylguanosine-trna-modification-promotes-esophageal-3e91c6m6.pdf

N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis

Purpose: Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) in esophageal squamous cell carcinoma (ESCC). Experimental Design: In a retrospective study, the prognostic significance of G-NchiRNA was determined in ESCC tissues. The correlation between seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-NchiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS). Results: Exosomal G-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n = 220) and a validation cohort (n = 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation. Conclusions: SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.

/pdf/evaluation-of-salivary-exosomal-chimeric-golm1-naa35-rna-as-wqhqvdchym.pdf

Evaluation of Salivary Exosomal Chimeric GOLM1-NAA35 RNA as a Potential Biomarker in Esophageal Carcinoma.

A novel systemic immune-inflammation index (SII) based on platelet (P), neutrophil (N), and lymphocyte (L) counts has been reported to be associated with clinical outcomes in several solid tumors. We aimed to investigate its prognostic value in esophageal squamous cell carcinoma (ESCC) and the potential relationship with quality of life (QOL). A total of 280 ESCC patients who underwent esophagectomy were enrolled. SII (SII = P × N/L) was calculated on the basis of data obtained within 1 week before surgery. An optimal cut-off value stratified patients into high (≥560) and low (<560) preoperative SII groups. The widely used EORTC QLQ-C30 and QLQ-OES18 were utilized to assess QOL at cancer diagnosis and 36 months after surgery. Generalized estimating equations (GEEs) were used to evaluate the association of SII with QOL. Kaplan–Meier method and Cox proportional regression were used to analyze the prognostic value of SII. Kaplan–Meier analyses revealed that higher SII correlated significantly with poorer overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001) in patients with ESCC. Multivariate analysis identified SII as an independent prognostic factor for OS (p < 0.001; HR 2.578; 95% CI 1.625–4.088) and DFS (p < 0.001; HR 2.699; 95% CI 1.726–4.223). In addition, patients with high SII exhibited notably deteriorating QOL (p < 0.05). The preoperative SII is a promising biomarker for predicting survival and QOL of patients with ESCC. It may help to identify the high-risk patients for treatment strategy decisions.

A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma.

OBJECTIVES: The demographic and clinicopathologic factors associated with 5-year survivors have not been well documented in oesophageal squamous cell carcinoma (OSCC). We evaluated factors predictive of actual 5-year survival in the present research. METHODS: We analysed 1241 patients underwent oesophagectomy for invasive OSCC retrospectively. The demographic and clinicopathologic characteristics were compared between patients who were alive >5 years after oesophagectomy and patients who died within 5 years of oesophagectomy. RESULTS: Univariate analysis showed significant differences between the two groups regarding 11 different factors. Further analysis by logistic regression showed that eight factors were identified as independent predictors of actual 5-year survival. CONCLUSIONS: The independent positive predictors for actual 5-year survival are younger patients, female gender, absence of weight loss, R0 resection, lower pathological T stage, lower pathological N stage, higher histologic grade and more resected lymph nodes.

/pdf/which-factors-are-associated-with-actual-5-year-survival-of-2l3nyvsqe4.pdf

Which factors are associated with actual 5-year survival of oesophageal squamous cell carcinoma?

Recently we published an article entitled ‘Which factors are associated with actual 5-year survival of oesophageal squamous cell carcinoma?’ [1]. It pleased us that V. P. Rao was concerned by our paper. He believed that it was inappropriate to adopt logistic regression for statistical analysis, and that one should adopt Cox regression [2]. Actually, this study was not a complete analysis of survival. Its purpose was to identify factors associated with actual five-year survival, instead of prognostic factors of patients with ESCC. So, in the present research, only two groups were identified and compared, including those patients who survived more than five years after oesophagectomy and those patients who died within five years. In other words, we presumed that patients with one-year survival were equivalent to patients with three-year survival because all of these patients died within five years. Similarly, we presumed that patients with six-year survival were equivalent to patients with eight-year survival because all of these patients survived more than five years. Therefore, in this study, survival data was a dichotomous variable. We consulted the statistical experts at our university again and they believed that logistic regression might be a better statistical method for investigating the relationship of dichotomous variable and some impact factors.

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Which factors are associated with actual 5-year survival of oesophageal squamous cell carcinoma?

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