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The occurrence of fungal infection seriously affects the survival and life quality of transplanted patients. The accurate diagnosis is of particular importance in the early stage of infection. To develop a novel diagnostic method for this kind of patient, we established a post-transplant immunosuppressed mice model with fungus inoculation and collected their peripheral blood at specific time points after infection. After screening by microarray, differentially expressed miRNAs and lncRNAs were selected and homologously analyzed with those of human beings from the gene database. These miRNAs and lncRNAs candidates were validated by qRT-PCR in peripheral blood samples from transplanted patients. We found that, compared with normal transplanted patients, the levels of miR-215 and miR-let-7 c were up-regulated in the plasma of patients with fungal infection (P

Yiwen Guo,1– 3,* Weixin Luo,1– 3,* Shanzhou Huang,4,* Wenting Zhao,5 Huadi Chen,1– 3 Yihao Ma,1– 3 Maodong Ye,1– 3 Yu Nie,1– 3 Yixi Zhang,6 Changjun Huang,1– 3 Qi Zhou,7,8 Xiaoshun He,1– 3 Maogen Chen1– 3 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, People’s Republic of China; 4Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 5School of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangzhou, 510515, People’s Republic of China; 6Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100005, People’s Republic of China; 7Department of General Surgery, Hui Ya Hospital of The First Affiliated Hospital, Sun Yat-sen University, Huizhou, Guangdong, 516081, People’s Republic of China; 8Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maogen Chen; Xiaoshun HeOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, People’s Republic of ChinaTel +86-18122731962; +86-20-87306082Fax +86-20-87306082Email gdtrc@163.com; chenmg3@mail.sysu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Identifying specific molecular markers that can predict HCC prognosis is extremely important. The protein deoxythymidylate kinase (DTYMK) has been reported to contribute to unfavorable prognosis in non-small cell lung cancer patients, but its role in the prediction of HCC patient prognosis has not been clarified.Methods: Samples from the TCGA and GEO databases were consecutively enrolled for gene expression analysis, clinicopathology analysis, immune microenvironment analysis and chemotherapeutic response prediction. The results were validated using 86 samples from the First Affiliated Hospital of Sun Yat-sen University. Cox regression analysis was used to analyze the effect of DTYMK on progression-free survival (PFS) and overall survival (OS). Functional enrichment analysis was used to describe the marker pathways that were significantly related to DTYMK. TIMER (Tumor Immune Estimation Resource), TISIDB (Tumor and Immune System Interaction DataBase) and CIBERSORT (Cell type Identification By Estimating Relative Subsets Of RNA Transcripts) were used to explore the immune microenvironment.Results: We found that DTYMK expression upregulation is associated with poor prognosis in HCC patients and tightly related to the pathways regulating the cell cycle and acid metabolism. Our findings revealed that hepatocellular carcinoma cell lines with high DTYMK expression were more sensitive to sorafenib and many other chemotherapeutic drugs. We also found an inhibiting effect of DTYMK on the immune microenvironment in the process of tumorigenesis.Discussion: We found that DTYMK has potential as a new prognostic and chemotherapeutic response biomarker for HCC patients and correlates with the immune microenvironment in HCC. However, there are some deficiencies in our study. First, this is a retrospective study that may lead to selection bias. Second, the protein expression of DTYMK was investigated via immunohistochemical analysis. Finally, we did not explore the exact underlying molecular mechanisms of DTYMK in tumorigenesis in this study, which is needed to be clarified in future research.Keywords: hepatocellular carcinoma, DTYMK, cell cycle, immune infiltration, TCGA

BACKGROUND: To explore the relationship between early allograft dysfunction (EAD) and post-reperfusion liver appearance, and to develop image-based models which predict EAD and short-term mortality. METHODS: A total of 351 recipients of liver transplant were enrolled and divided into training set and testing set. Liver images of post-reperfusion donors and clinical information were collected. All the images were preprocessed. Support vector machines (SVM) and convolution neural network (CNN) models based on the texture analysis of post-reperfusion liver RGB images were constructed to predict EAD. Then, the model with a better performance was selected to construct further predictive models with additional inputs of clinical information. In addition, a score, namely image score, was assigned to each liver image based on the prediction probability from the CNN model. Further, the comparisons of outcomes among different image scores were performed. RESULTS: Out of the 351 enrolled recipients, 229 were in the training set while 122 in the testing set. CNN model achieved an AUC of 0.709 in testing set, outperforming the SVM model which has an AUC of 0.661. Further predictive model was based on the framework of the CNN model, where an AUC of 0.727 was obtained. Moreover, the lager image score was found to be relative to more postoperative infusion, more postoperative complication, the longer length of ICU and hospital stay. CONCLUSION: The post-reperfusion appearance of donor liver was associated with the occurrence of EAD. Moreover, it was feasible to predict EAD and patient outcomes through the texture analysis of post-reperfusion liver RGB images.

Long non‑coding RNAs (lncRNAs) serve a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. Certain studies have focused on lncRNA nuclear enriched abundant transcript 1 (NEAT1) in HCC. However, the relationship between lncRNA NEAT1 and HCC remains unclear. The present study found that NEAT1 was significantly overexpressed in HCC cell lines compared with LX‑2 hepatic stellate cells. NEAT1 expression in Huh7 and MHCC‑97H cells was increased following transfection with lentivirus (LV)‑NEAT1 but inhibited by LV‑short hairpin NEAT1. Knockdown of NEAT1 significantly repressed HCC cell viability, increased cell apoptosis, and inhibited cell migration and invasion capacity. By contrast, upregulation of NEAT1 demonstrated the reverse effects. Furthermore, microRNA‑320a (miR‑230a) was predicted to be a direct target of NEAT1 and was significantly reduced in HCC cells. Additionally, a luciferase activity reporter assay and RNA immunoprecipitation assay were performed to confirm the interaction between miR‑320a and NEAT1. Using a dual‑luciferase activity assay, L antigen family member 3 (LAGE3) was found to be a target of miR‑320a. Finally, in vivo nude mouse models were established, and the results indicated that NEAT1 suppressed HCC progression by targeting miR‑320a. In conclusion, the present findings revealed that the NEAT1/miR‑320a/LAGE3 axis participates in HCC development and that NEAT1 could be used as a biomarker for HCC.

Background MicroRNAs (miRNAs) play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. However, the relationship between miR-497-5p and HCC remains unclear. Methods Kaplan–Meier curve analysis and the log-rank test were used to investigate the efficacy of miR-497-5p on overall survival (OS) and disease-free survival (DFS) in patients with HCC. According to in vitro experiments, programmed cell death 4 (PDCD4) was a target of miR-497-5p by the dual-luciferase activity assay. The efficacy of PDCD4 on cell proliferation and metastasis in HCC was examined by transwell assays, CCK-8 assays and reverse transcription quantitative PCR (RT-qPCR). Additionally, we conducted a luciferase activity reporter assay to confirm the interaction between lncRNA XIST and miR-49-5p. Then, to evaluate the relationship between lncRNA XIST and miR-497-5p, several mechanistic experiments, including qRT-PCR, Western blotting, transwell assays and tumor xenograft assays, were performed. Results miR-497-5p was upregulated in HCC tissues, and high expression of miR-497-5p resulted in increases in tumor size and tumor number and a higher tumor-node-metastasis (TNM) stage and Edmondson grade in patients with HCC. Silencing miR-497-5p inhibited the proliferation and migration of HCC cells. PDCD4, which was downregulated in HCC tissues, was shown to be a target of miR-497-5p and was negatively correlated with the expression of miR-497-5p. lncRNA XIST was found to act as a miR-497-5p sponge and to regulate the level of PDCD4, which is targeted by miR-497-5p. lncRNA XIST was observed to be downregulated in the HCC tissues and positively correlated with the expression of PDCD4. Conclusions Our findings reveal that the XIST/miR-497-5p/PDCD4 axis participates in HCC development and that XIST could be used as a biomarker of HCC.