PURPOSE This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue ( P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis ( P < .05). CONCLUSION The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.

Background Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM, STC2, NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions Prognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.

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Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients. Importantly, the decreased DBCCR1 was found correlated with more advanced stages of cancer, and with a significantly shorter survival of patients. Genetic silencing DBCCR1 in human lung cancer cell line A549 resulted in an enhanced proliferation, migration, and invasion capacity. Conversely, restoring DBCCR1 expression blocked the growth and inhibited the ability of cancer cell in migration and invasion. Interestingly, DBCCR1 attenuates the expression of DNMT1 (DNA methyltransferase 1), suggesting a reciprocal regulation between genetic silencing of cancer suppressor genes and activating DNA methylation. Our data thus implicates DBCCR1 downregulation as a potential module in the pathogenesis of lung cancer through DNA methylation.

Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. Methods: We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. Results: The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusion: These molecules may serve as potential therapeutic targets and biomarkers for the new-immunotherapy of EC.

Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods: This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results: We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions: These molecules may serve as potential therapeutic targets and biomarkers for the new-immunotherapy of EC.

Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods: This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results: We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions: Prognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.