law firm, and other from Equity Quotient outside the submitted work. Dr Jagsi serves on the board of directors of ASCO and as vice chair of the ethics committee of ASTRO. This work is entirely separate from those roles. No other disclosures were reported.

BackgroundPlenty of studies have demonstrated the prognostic value of various inflammation-based indexes in cancer. This study was designed to investigate the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in esophageal squamous cell carcinoma.MethodsA retrospective study of 423 cases with newly diagnosed esophageal squamous cell carcinoma was conducted. We analyzed the association of the CRP/Alb ratio with clinicopathologic characteristics. The prognostic value was explored by univariate and multivariate survival analysis. In addition, we compared the discriminatory ability of the CRP/Alb ratio with other inflammation-based prognostic scores by evaluating the area under the receiver operating characteristics curves (AUC), including the modified Glasgow Prognostic Score (mGPS), neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR).ResultsThe optimal cut-off value was identified to be 0.095 for the CRP/Alb ratio. A higher level of the CRP/Alb ratio was associated with larger tumor size (P < 0.001), poorer differentiation (P = 0.019), deeper tumor invasion (P = 0.003), more lymph node metastasis (P = 0.015), more distant metastasis (P < 0.001) and later TNM stage (P < 0.001). The CRP/Alb ratio was identified to be the only inflammation-based prognostic score with independent association with overall survival by multivariate analysis (P = 0.031). The AUC value of the CRP/Alb ratio was higher compared with the NLR and PLR, but not mGPS at 6, 12 and 24 months of follow-up. In addition, the CRP/Alb ratio could identify a group of patients with mGPS score of 0 who had comparable overall survival with those with mGPS score of 1.ConclusionsThe CRP/Alb ratio is a novel but promising inflammation-based prognostic score in esophageal squamous cell carcinoma. It is a valuable coadjutant for the mGPS to further identify patients’ survival differences.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1379-6) contains supplementary material, which is available to authorized users.

BackgroundMelatonin is a pleiotropic signaling molecule that plays multifarious roles in plants stress tolerance. The polyamine (PAs) metabolic pathway has been suggested to eliminate the effects of environmental stresses. However, the underlying mechanism of how melatonin and PAs function together under heat stress largely remains unknown. In this study, we investigated the potential role of melatonin in regulating PAs and nitric oxide (NO) biosynthesis, and counterbalancing oxidative damage induced by heat stress in tomato seedlings.ResultsHeat stress enhanced the overproduction of reactive oxygen species (ROS) and damaged inherent defense system, thus reduced plant growth. However, pretreatment with 100 μM melatonin (7 days) followed by exposure to heat stress (24 h) effectively reduced the oxidative stress by controlling the overaccumulation of superoxide (O2•−) and hydrogen peroxide (H2O2), lowering the lipid peroxidation content (as inferred based on malondialdehyde content) and less membrane injury index (MII). This was associated with increased the enzymatic and non-enzymatic antioxidants activities by regulating their related gene expression and modulating the ascorbate–glutathione cycle. The presence of melatonin induced respiratory burst oxidase (RBOH), heat shock transcription factors A2 (HsfA2), heat shock protein 90 (HSP90), and delta 1-pyrroline-5-carboxylate synthetase (P5CS) gene expression, which helped detoxify excess ROS via the hydrogen peroxide-mediated signaling pathway. In addition, heat stress boosted the endogenous levels of putrescine, spermidine and spermine, and increased the PAs contents, indicating higher metabolic gene expression. Moreover, melatonin-pretreated seedlings had further increased PAs levels and upregulated transcript abundance, which coincided with suppression of catabolic-related genes expression. Under heat stress, exogenous melatonin increased endogenous NO content along with nitrate reductase- and NO synthase-related activities, and expression of their related genes were also elevated.ConclusionsMelatonin pretreatment positively increased the heat tolerance of tomato seedlings by improving their antioxidant defense mechanism, inducing ascorbate–glutathione cycle, and reprogramming the PAs metabolic and NO biosynthesis pathways. These attributes facilitated the scavenging of excess ROS and increased stability of the cellular membrane, which mitigated heat-induced oxidative stress.Electronic supplementary materialThe online version of this article (10.1186/s12870-019-1992-7) contains supplementary material, which is available to authorized users.

Background: Tumor mutational burden (TMB) has been widely studied as a predictive biomarker of response to immune checkpoint inhibitors (ICIs). Besides, evidence suggests frameshift indels are a highly immunogenic mutational class and thus a potentially superior biomarker. However, the general prognostic impact of TMB and indel burden in patients with solid tumors has not been systematically investigated. Methods:We analyzed 20 primary solid cancer types from The Cancer Genome Atlas (TCGA) database.Clinicopathologic factors, TMB and indel burden were collected or calculated. For each cancer type, the impact of TMB or indel burden on overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression with the method of inverse probability of treatment weighting.Results: Twenty cancer types from 6,035 patients were analyzed. Survival analysis showed that TMB had a significant impact on OS in 14 out of these 20 cancer types. According to the general survival impact of TMB, they could be classified into three groups, namely the TMB-Worse (eight cancer types), TMB-Better (six cancer types) and TMB-Similar (six cancer types) group, in which higher TMB was associated with inferior, superior, or similar OS, respectively. The survival impacts of TMB in the TMB-Worse and TMB-Better groups were generally consistent when limited to genes from two FDA-approved panels. Notably, in two out of the six cancer types in the TMB-Similar group, the indel burden significantly affected OS.Conclusions: TMB, as well as indel burden, has divergent prognostic impact in different cancer types, thus could be incorporated in prognostication and risk stratification. More importantly, the general prognostic impact should be taken into account when establishing the predictive function of TMB to ICI treatment.

Key Points Question What are the profiles of cancer risk associated with immune-mediated diseases? Findings In this cohort study of 478 753 participants, immune-mediated diseases were associated with an increased risk of total cancer. Organ-specific immune-mediated diseases had stronger associations with risk of local cancers than extralocal cancers, and many immune-mediated diseases were associated with increased risk of cancer in the involved organs and in the near and distant organs or different systems. Meaning The findings suggest that immune-mediated diseases are associated with risk of cancer at the local and systemic levels, supporting the role of local and systemic immunoregulation in carcinogenesis.