Elevated preoperative NLR is an independent predictor of worse RFS for patients with stage IIA colon cancer and a potential biomarker to identify candidates for adjuvant chemotherapy.

BackgroundExpansions of myeloid-derived suppressor cells (MDSCs) have been identified in human solid tumors, including colorectal cancer (CRC). However, the nature of these tumor-associated MDSCs and their interactions with tumor cells in CRC are still poorly understood.MethodsThe percentages and phenotype of MDSCs in peripheral blood and tumorous and paraneoplastic tissues from CRC patients, as well as the clinical relevance of these MDSCs, were assessed. Age-matched healthy donors were included as controls. The interaction between MDSCs and T cells or tumor cells was investigated in a coculture system in vitro, and the molecular mechanism of the effect of MDSCs on T cells or tumor cells was evaluated.ResultsWe discovered that CRC patients had elevated levels of CD33+CD11b+HLA-DR− MDSCs in primary tumor tissues and in peripheral blood, and the elevated circulating MDSCs were correlated with advanced TNM stages and lymph node metastases. Radical resection significantly decreases the proportions of circulating MDSCs and CD4+CD25highFOXP3+ regulatory T cells. In vitro, CRC cells mediate the promotion of MDSC induction. Moreover, these tumor-induced MDSCs could suppress T cell proliferation and promote CRC cell growth via cell-to-cell contact. Such effects could be abolished by the inhibition of oxidative metabolism, including the production of nitric oxide (NO), and reactive oxygen species (ROS).ConclusionsOur results reveal the functional interdependence between MDSCs, T cells and cancer cells in CRC pathogenesis. Understanding the impact of MDSCs on T cells and tumor cells will be helpful to establish an immunotherapeutic strategy in CRC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0410-7) contains supplementary material, which is available to authorized users.

Purpose: Neoadjuvant chemoradiotherapy (neoCRT) is a standard treatment for locally advanced rectal cancer (LARC); however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to identify factors involved in the radioresistance of colorectal cancer and to clarify the underlying mechanisms.Experimental Design: A genome-wide RNAi screen was used to search for candidate radioresistance genes. After RFC4 knockdown or overexpression, colorectal cancer cells exposed to X-rays both in vitro and in a mouse model were assayed for DNA damage, cytotoxicity, and apoptosis. Moreover, the regulatory effects and mechanisms of RFC4 in DNA repair were investigated in vitro. Finally, the relationships between RFC4 expression and clinical parameters and outcomes were investigated in 145 patients with LARC receiving neoCRT.Results: RFC4, NCAPH, SYNE3, LDLRAD2, NHP2, and FICD were identified as potential candidate radioresistance genes. RFC4 protected colorectal cancer cells from X-rayinduced DNA damage and apoptosis in vitro and in vivo. Mechanistically, RFC4 promoted nonhomologous end joining (NHEJ)-mediated DNA repair by interacting with Ku70/ Ku80 but did not affect homologous recombination-mediated repair. Higher RFC4 expression in cancer tissue was associated with weaker tumor regression and poorer prognosis in patients with LARC treated with neoCRT, which likely resulted from the effect of RFC4 on radioresistance, not chemoresistance.Conclusions: RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in colorectal cancer cells. In addition, the expression level of RFC4 predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in patients with LARC.

From the result of this study, we could learn that celecoxib could reduce HFS that was induced by capecitabine. So we recommend that celecoxib can be used in capecitabine-based chemotherapy.

More than 98% of the human genome does not encode proteins, and the vast majority of the noncoding regions have not been well studied. Some of these regions contain enhancers and functional non-coding RNAs. Previous research suggested that enhancer transcripts could be potent independent indicators of enhancer activity, and some enhancer lncRNAs (elncRNAs) have been proven to play critical roles in gene regulation. Here, we identified enhancer–promoter interactions from high-throughput chromosome conformation capture (Hi-C) data. We found that elncRNAs were highly enriched surrounding chromatin loop anchors. Additionally, the interaction frequency of elncRNA-associated enhancer–promoter pairs was significantly higher than the interaction frequency of other enhancer–promoter pairs, suggesting that elncRNAs may reinforce the interactions between enhancers and promoters. We also found that elncRNA expression levels were positively correlated with the interaction frequency of enhancer–promoter pairs. The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. Interestingly, G-quadruplexes were found to potentially mediate some enhancer–promoter interaction pairs, and the interaction frequency of these pairs was significantly higher than that of other enhancer–promoter pairs. We also found that the G-quadruplexes on enhancers were highly related to the expression of elncRNAs. G-quadruplexes located in the promoters of elncRNAs led to high expression of elncRNAs, whereas G-quadruplexes located in the gene bodies of elncRNAs generally resulted in low expression of elncRNAs.