There is significant void in establishing validated non-invasive surrogate biomarkers of liver fibrosis/cirrhosis in chronic liver diseases (CLD). Golgi protein 73 (GP73) has been suggested as a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, significant background of cirrhosis could have accounted for the elevation of serum GP73 in HCC. In this study, we have taken advantage of a well-defined extensive cohort of 3044 patients with either compensated cirrhosis (n = 1247), decompensated cirrhosis (n = 841) or pre-cirrhotic CLD (n = 956) and our ability to quantify serum GP73 to define the potential of serum GP73 as a biomarker of liver cirrhosis/fibrosis in CLD. The diagnostic value of GP73 was compared with aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and liver stiffness measurement (LSM). Immunohistochemical analysis was performed to measure hepatic GP73 expression. Receiver operating characteristic curve analysis demonstrated that serum GP73 had a good diagnostic potential for compensated cirrhosis regardless of etiology. The diagnostic performance of GP73 is better than APRI, FIB-4 and similar with LSM, especially in patients with severe inflammation, steatosis and cholestasis. Notably, in patients of autoimmune liver diseases, non-alcoholic fatty liver disease and viral hepatitis, serum GP73 also exhibited diagnostic value for advanced fibrosis as well as cirrhosis. Furthermore, there is also a gradual increase in GP73 expression with disease progression from mild fibrosis to cirrhosis. In conclusion, GP73 is an effective and reliable serological marker for the diagnosis of advanced fibrosis and prediction of appearance of cirrhosis.

The CRISPR/Cas9 system is a novel genome editing technology which has been successfully used to inhibit HBV replication. Here, we described a novel gRNA-microRNA (miRNA)-gRNA ternary cassette driven by a single U6 promoter. With an anti-HBV pri-miR31 mimic integrated between two HBV-specific gRNAs, both gRNAs could be separated from the long transcript of gRNA-miR-HBV-gRNA ternary cassette through Drosha/DGCR8 processing. The results showed that the gRNA-miR-HBV-gRNA ternary cassette could efficiently express two gRNAs and miR-HBV. The optimal length of pri-miRNA flanking sequence in our ternary cassette was determined to be 38 base pairs (bp). Besides, HBV-specific gRNAs and miR-HBV in gRNA-miR-HBV-gRNA ternary cassette could exert a synergistic effect in inhibiting HBV replication and destroying HBV genome in vitro and in vivo. Most importantly, together with RNA interference (RNAi) approach, the HBV-specific gRNAs showed the potent activity on the destruction of HBV covalently closed circular DNA (cccDNA). Since HBV cccDNA is an obstacle for the elimination of chronic HBV infection, the gRNA-miR-HBV-gRNA ternary cassette may be a potential tool for the clearance of HBV cccDNA.

Background: Chromobox 3 (CBX3) is a member of the chromobox family proteins, which plays a critical role in tumor progression, but the exact function of CBX3 in gastric cancer remains unknown. The current research mainly investigates the underlying mechanisms and clinical value of CBX3 in gastric cancer. Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of CBX3 in gastric cancer. CBX3 expression was further determined by immunohistochemistry (IHC). The function of CBX3 on proliferation, migration and the cell cycle was explored via colony-forming, cell cycle and transwell assays, respectively. Moreover, RNA sequencing (RNA-seq) in AGS cells and two cohorts was utilized to explore the specific mechanism of CBX3. Results: CBX3 expression was upregulated in human gastric cancer tissues and the expression level was closely associated with adverse signs. Knockdown of CBX3 in gastric cancer cells significantly inhibited the malignant phenotype. In addition, RNA-seq analysis revealed that CBX3 regulates genes related to the cell cycle, mismatch repair and immune-related pathways. Furthermore, the expression of CBX3 was significantly and inversely related to the abundance of tumor-infiltrating lymphocytes (TILs), PDCD1 and PDCD1LG2 expression and immunotherapy responses. Moreover, CBX3 influences the effectiveness of chemotherapy, thereby impacting the prognosis of gastric cancer patients. Conclusion: CBX3 contributes to gastric cancer progression and is associated with chemotherapy and immunotherapy response. CBX3 may serve as a new diagnostic biomarker and potential target for immunotherapy and chemotherapy in gastric cancer.

The aim of this study was to explore the most powerful systemic inflammation marker of survival in locally advanced rectal cancer (LARC) patients and construct prognostic nomograms. A total of 472 LARC patients undergoing neoadjuvant chemoradiotherapy (NCRT) and radical surgery from 2011 to 2015 were included. The optimal cutoff points for the systemic immune-inflammation index (SII); and neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios were calculated and determined by using the X-tile program. The cutoff values were 797.6. 2.3, 169.5, and 0.4, respectively. Cox regression analysis demonstrated that higher pathological TNM stage, the AJCC tumor regression grade, and the NLR level were significantly associated with increased overall survival and disease-free survival. High NLR level (≥ 2.3) was associated with higher pre-NCRT CA19-9 levels, lower hemoglobin, larger tumor size, and more lymph nodes retrieved (p = 0.012, p = 0.024, and p < 0.001; p < 0.001, respectively). High NRL scores were associated with poorer 5-year diseasefree survival and overall survival (p < 0.001, and p < 0.001, respectively). Predictive nomograms and time-independent receiver operating characteristic (ROC) curve that included the NLR score group were superior to those without NLR scores. Higher NLR scores (≥2 0.3) were associated with poorer DFS and OS in LARC patients. In addition, NLR was identified as the most effective marker for systemic inflammation, and the prognostic value was further confirmed by time-dependent ROC analysis. More intense adjuvant treatment could be considered for higher nLR score patients with LARc following ncRt. The standard of care for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). This strategy offers a higher probability of tumor downsizing and downstaging, increased tumor resectability, and better local tumor control 1-3. However, patients show a wide variation in responses to NCRT and thus, different oncological outcomes. Currently, it remains difficult to accurately predict treatment outcomes for LARC patients after NCRT. The identification of reliable biomarkers for the oncologic outcomes is important to assist in risk-adapted treatment strategies and subsequent surveillance. The systematic inflammatory response is involved in the development, progression, treatment response, and prognosis of many cancers, including prostate, breast, and colorectal cancers (CRC) 4-6. Accumulating evidence has demonstrated an association of systematic inflammation and resistance to radiotherapy and chemotherapy in CRC 7-9. The systematic inflammatory response can be reflected by hematological parameters, including the systemic immune-inflammation index (SII), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR). Several studies have revealed that the hematological inflammatory markers could be predictive markers for oncolo...

Leukaemia is the most common malignancy in children and one of the most common malignancies in young adults. Acute myeloid leukaemia is often associated with early oral manifestations. The purpose of this study is to report the case of a 49-year-old male with spontaneous gingival bleeding for over two years with undiagnosed leukaemia. Haematological investigation was instigated and on referral to the Haematology Department at Dunedin Public Hospital, the diagnosis of an acute myeloid leukaemia was confirmed. Since oral lesions can be one of the early events of acute myeloid leukaemia, they may be considered as an important diagnostic indicator for oral health practitioners, and their roles in diagnosing and treating such patients.

No abstract

Background. Pyroptosis has been confirmed as a type of inflammatory programmed cell death in recent years. However, the prognostic role of pyroptosis in colon cancer (CC) remains unclear. Methods. Dataset TCGA-COAD which came from the TCGA portal was taken as the training cohort. GSE17538 from the GEO database was treated as validation cohorts. Differential expression genes (DEGs) between normal and tumor tissues were confirmed. Patients were classified into two subgroups according to the expression characteristics of pyroptosis-related DEGs. The LASSO regression analysis was used to build the best prognostic signature, and its reliability was validated using Kaplan–Meier, ROC, PCA, and t-SNE analyses. And a nomogram based on the multivariate Cox analysis was developed. The enrichment analysis was performed in the GO and KEGG to investigate the potential mechanism. In addition, we explored the difference in the abundance of infiltrating immune cells and immune microenvironment between high- and low-risk groups. And we also predicted the association of common immune checkpoints with risk scores. Finally, we verified the expression of the pyroptosis-related hub gene at the protein level by immunohistochemistry. Results. A total of 23 pyroptosis-related DEGs were identified in the TCGA cohort. Patients were classified into two molecular clusters (MC) based on DEGs. Kaplan–Meier survival analysis indicated that patients with MC1 represented significantly poorer OS than patients with MC2. 13 overall survival- (OS-) related DEGs in MCs were used to construct the prognostic signature. Patients in the high-risk group exhibited poorer OS compared to those in the low-risk group. Combined with the clinical features, the risk score was found to be an independent prognostic factor of CC patients. The above results are verified in the external dataset GSE17538. A nomogram was established and showed excellent performance. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the varied prognostic performance between high- and low-risk groups may be related to the immune response mediated by local inflammation. Further analysis showed that the high-risk group has stronger immune cell infiltration and lower tumor purity than the low-risk group. Through the correlation between risk score and immune checkpoint expression, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) was predicted as a potential therapeutic target for the high-risk group. Conclusion. The 13-gene signature was associated with OS, immune cells, tumor purity, and immune checkpoints in CC patients, and it could provide the basis for immunotherapy and predicting prognosis and help clinicians make decisions for individualized treatment.

No abstract