BACKGROUNDIn recent decades, neoadjuvant therapy (NT) has been the standardized treatment for locally advanced rectal cancer (LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response (pCR). If the pathological response (PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore, developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients.AIMTo establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC.METHODSRectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0 (ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens (capecitabine/deGramont-RT, mFOLFOX6, and mFOLFOX6-RT) to predict pCR probability.RESULTSFour hundred and three patients were included in this study; 72 (17.9%) had pCR at the final pathology report, and 177 (43.9%) achieved good downstaging to ypT0-2N0M0 (ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia (MRF) status, and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio (NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the mFOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation.CONCLUSIONWe established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.

To assess changes of metabolite content and regulation mechanism of the phenolic acid biosynthesis pathway at different developmental stages of leaves, this study performed a combined metabolome and transcriptome analysis of Cyclocarya paliurus leaves at different developmental stages. Metabolite and transcript profiling were conducted by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer and high-throughput RNA sequencing, respectively. Transcriptome identification showed that 58 genes were involved in the biosynthesis of phenolic acid. Among them, 10 differentially expressed genes were detected between every two developmental stages. Identification and quantification of metabolites indicated that 14 metabolites were located in the phenolic acid biosynthetic pathway. Among them, eight differentially accumulated metabolites were detected between every two developmental stages. Association analysis between metabolome and transcriptome showed that six differentially expressed structural genes were significantly positively correlated with metabolite accumulation and showed similar expression trends. A total of 128 transcription factors were identified that may be involved in the regulation of phenolic acid biosynthesis; these include 12 MYBs and 10 basic helix–loop–helix (bHLH) transcription factors. A regulatory network of the phenolic acid biosynthesis was established to visualize differentially expressed candidate genes that are involved in the accumulation of metabolites with significant differences. The results of this study contribute to the further understanding of phenolic acid biosynthesis during the development of leaves of C. paliurus.

BackgroundNumerous cancer types present the aberrant TANK-binding kinase 1 (TBK1) expression, which plays an important role in driving inflammation and innate immunity. However, the prognostic role of TBK1 and its relationship with immune cell infiltration in hepatocellular carcinoma (HCC) remain unclear.MethodsThe expression and prognostic value of TBK1 was analyzed by Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and further confirmed in the present cohort of patients with HCC. The association between TBK1 and HCC immune infiltrates, and its potential mechanism were investigated via analyses of the Tumor Immune Estimation Resource, tumor-immune system interactions database (TISIDB), CIBERSORT, STRING, and Metascape. The effect of TBK1 on immune infiltrates and the therapeutic value of targeting TBK1 were further investigated in a HCC mouse model by treatment with a TBK1 antagonist.ResultsThe level of TBK1 expression in HCC was higher than that measured in normal tissues, and associated with poorer overall survival (GEPIA: hazard ratio [HR]=1.80, P=0.038; Kaplan–Meier plotter: HR=1.87, P<0.001; CPTAC: HR=2.23, P=0.007; Our cohort: HR=2.92, P=0.002). In addition, high TBK1 expression was found in HCC with advanced TNM stage and identified as an independent poor prognostic factor for overall survival among patients with HCC. In terms of immune infiltration, tumor tissues from HCC patients with high TBK1 expression had a low proportion of CD8+ T cells, and TBK1 expression did not show prognostic value in HCC patients with enriched CD8+ T cells. Furthermore, TBK1 expression was positively correlated with the markers of T cell exhaustion and immunosuppressive cells in the HCC microenvironment. Mechanistically, the promotion of HCC immunosuppression by TBK1 was involved in the regulation of inflammatory cytokines. In vivo experiments revealed that treatment with a TBK1 antagonist delayed HCC growth by increasing the number of tumor-infiltrating CD8+ T cells.ConclusionsThe up-regulated expression of TBK1 may be useful in predicting poor prognosis of patients with HCC. In addition, TBK1, which promotes the HCC immunosuppressive microenvironment, may be a potential immunotherapeutic target for patients with HCC.

In recent years, the diagnosis and treatment of colorectal cancer (CRC) have been continuously improved, but the mortality rate continues to be high, especially in advanced patients. CRC patients usually have no obvious symptoms in the early stage and are already in the advanced stage when they are diagnosed. The 5-year survival rate is only 10%. The blood markers currently used to screen for CRC, such as carcinoembryonic antigen and carbohydrate antigen 19-9, have low sensitivity and specificity, whereas other methods are invasive or too expensive. As a result, recent research has shifted to the development of minimally invasive or noninvasive biomarkers in the form of body fluid biopsies. Non-coding RNA molecules are composed of microRNAs, long non-coding RNAs, small nucleolar RNAs, and circular RNAs, which have important roles in the occurrence and development of diseases and can be utilized for the early diagnosis and prognosis of tumors. In this review, we focus on the latest findings of mRNA-ncRNA as biomarkers for the diagnosis and prognosis of CRC, from fluid to tissue level.