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BackgroundInflammation-based prognostic scores such as the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), Glasgow prognostic score (GPS), and modified GPS (mGPS) have been reported to have prognostic value in patients with many types of cancer, including esophageal squamous cell carcinoma (ESCC). However, the role of the C-reactive protein/Albumin (CRP/Alb) ratio in ESCC has not yet been evaluated.MethodsA total of 468 patients suffering from histologically proven ESCC were enrolled between January 2000 and July 2010. The GPS, mGPS, NLR, PLR and CRP/Alb ratios were tested together with established prognostic factors in univariate and multivariate Cox regression analyses of overall survival (OS).ResultsThe optimal cutoff level for the CRP/Alb ratio was 0.50. The CRP/Alb ratio (continuous) had higher AUC values at 12 months (0.796), 24 months (0.805), and 36 months (0.815) than the NLR, GPS and mGPS. In univariate analysis, the 5-year OS rate for patients with a CRP/Alb ratio > 0.50 was 43.4%, while the rate for patients with a CRP/Alb ratio ≤ 0.50 was 17.7% (P < 0.0001). In multivariate analysis, patients with a CRP/Alb ratio > 0.50 had worse survival than patients with a CRP/Alb ratio ≤ 0.50 (HR: 2.44; 95% CI: 1.82–3.26; P < 0.0001).ConclusionIn summary, to the best of our knowledge, this is the first study to identify the CRP/Alb ratio as a novel inflammation-based prognostic factor in a large group of ESCC patients. The prognostic value of the CRP/Alb ratio needs to be verified in prospective multicenter studies.

The objective of the study was to investigate the expression and functions of CASC9 in esophageal squamous cell carcinoma (ESCC). Long noncoding RNAs (lncRNAs) upregulated in ESCC tissues were detected by RNA sequencing. Expression of CASC9 was determined from clinical samples and cell lines by qRT‐PCR. The effects of CASC9 knockdown on migration and invasion were evaluated by wound healing assay, cell migration and invasion assays in vitro. We found that the lncRNA, CASC9, was markedly upregulated in ESCC tissues. Furthermore, knockdown of CASC9 significantly suppressed cell migration and invasion in vitro. Furthermore, enhanced CASC9 expression level was correlated with differentiation. The results indicated that CASC9 is significantly upregulated in ESCC tissues and may represent a new marker of poor prognosis and a potential therapeutic target for esophageal cancer intervention.

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II–IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

Abstract. CDH1, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations. In an attempt to clarify the mechanism responsible for inactivation of this gene in carcinomas, we investigated the methylation status of the CDH1 gene 5'-cpG islands and its regulatory mechanism in the progression of esophageal squamous cell carcinoma. Real-time methylation-specific polymerase chain reaction (qMSP) and treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-cdR) were conducted to analyze the methylation status at the CDH1 promoter region in the human esophageal carcinoma cell lines, Ec1 and Ec9706. A total of 235 invasive esophageal squamous cell carcinomas (EScc) at stages I-IV and their corresponding normal tissue samples, were included in an immunohistochemistry study and methylation analysis of CDH1. The results demonstrate that in Ec1 and Ec9706 cells, the CDH1 promoter is methylated and treatment with 5-Aza-cdR restored CDH1 expression. Enhanced CDH1 expression decreased cell migration, invasion ability and increased adhesion ability. decreased CDH1 expression was detected in 59.6% of EScc tissues, compared with their adjacent non-neoplastic epithelia, which had a close correlation with the primary tumor status, lymph node status, distant metatasis and clinicopathologic stage. Hypermethylation at the CDH1 promoter was detected in 97.9% of 140 cases of EScc with low CDH1 expression. The methylation of CDH1 promoters (P=0.929) was closely correlated with the lack of expression of their corresponding proteins. The cox regression model for survival analysis showed that increases in CDH1 methylation had a greater impact on the prognosis than tumor clinical stage. These findings suggest that CDH1 gene silencing by promoter hypermethylation and the resultant reduction of CDH1 expression may play an important role in the progression of EScc. CDH1 methylation was a significant predictor of survival in EScc patients after surgery.

Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood.Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM.Results: The status of EGFR-activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM development.Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need.

Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.

These authors contributed equally to this work.