Radiomic advances in the transarterial chemoembolization related therapy for hepatocellular carcinoma.

Radiomics is a hot topic in the research on customized oncology treatment, efficacy evaluation, and tumor prognosis prediction. To achieve the goal of mining the heterogeneity information within the tumor tissue, the image features concealed within the tumoral images are turned into quantifiable data features. This article primarily describes the research progress of radiomics and clinical-radiomics combined model in the prediction of efficacy, the choice of treatment modality, and survival in transarterial chemoembolization (TACE) and TACE combination therapy for hepatocellular carcinoma.

Capsaicin receptor TRPV1 maintains quiescence of hepatic stellate cells in the liver via recruitment of SARM1.

BACKGROUND & AIMS: Capsaicin receptor, also known as transient receptor potential vanilloid 1 (TRPV1), is involved in pain physiology and neurogenic inflammation. Herein, we discovered the presence of TRPV1 in hepatic stellate cells (HSCs) and aimed to delineate its function in this cell type and liver fibrosis. METHODS: TRPV1 expression was examined in liver biopsies from patients with liver fibrosis using quantitative real-time PCR and immunostaining. Its contribution to liver fibrosis was examined in Trpv1-/- mice, upon lentiviral delivery of the TRPV1 gene, and in human and mouse primary HSCs, using patch clamp, intracellular Ca2+ mobilization determination, FACS analyses and gain/loss of function experiments. Binding of sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) to TRPV1 was determined using mass spectrometry, co-immunoprecipitation, surface plasmon resonance, bioluminescence resonance energy transfer, and NanoBiT. RESULTS: TRPV1 mRNA levels are significantly downregulated in patients with liver fibrosis and mouse models, showing a negative correlation with F stage and α-smooth muscle actin expression, a marker of HSC activation. TRPV1 expression and function decrease during HSC activation in fibrotic livers in vivo or during culture. Genetic and pharmacological inhibition of TRPV1 in quiescent HSCs leads to NF-κB activation and pro-inflammatory cytokine production. TRPV1 requires binding of its N-terminal ankyrin repeat domain to the TIR-His583 (Toll/interleukin-1 receptor) domain of SARM1 to prevent HSCs from pro-inflammatory activation. Trpv1-/- mice display increased HSC activation and more severe liver fibrosis, whereas TRPV1 overexpression is antifibrotic in various disease models. CONCLUSION: The antifibrotic properties of TRPV1 are attributed to the prevention of HSC activation via the recruitment of SARM1, which could be an attractive therapeutic strategy against liver fibrosis. IMPACT AND IMPLICATIONS: We identified the neuronal channel protein TRPV1 as a gatekeeper of quiescence in hepatic stellate cells, a key driver of liver fibrogenesis and chronic liver disease. Physiologically expressed in healthy liver and consistently downregulated during liver fibrosis development, its therapeutic re-expression is expected to have few side effects, making it an attractive target diagnostic tool and drug candidate for industry and clinicians.

Identification of predictive factors for post-transarterial chemoembolization liver failure in hepatocellular carcinoma patients: A retrospective study.

BACKGROUND: Post-transarterial chemoembolization (TACE) liver failure occurs frequently in hepatocellular carcinoma (HCC) patients. The identification of predictors for post-TACE liver failure is of great importance for clinical decision-making in this population. AIM: To investigate the occurrence rate and predictive factors of post-TACE liver failure in this retrospective study to provide clues for decision-making regarding TACE procedures in HCC patients. METHODS: The clinical records of HCC patients treated with TACE therapy were reviewed. Baseline clinical characteristics and laboratory parameters of these patients were extracted. Logistic models were used to identify candidates to predict post-TACE liver failure. RESULTS: A total of 199 HCC patients were enrolled in this study, and 70 patients (35.2%) developed post-TACE liver failure. Univariate and multivariate logistic models indicated that microspheres plus gelatin embolization and main tumor size > 5 cm were risk predictors for post-TACE liver failure [odds ratio (OR): 4.4, 95% confidence interval (CI): 1.2-16.3, P = 0.027; OR: 2.3, 95%CI: 1.05-5.3, P = 0.039, respectively]. Conversely, HCC patients who underwent tumor resection surgery before the TACE procedure had a lower risk for post-TACE liver failure (OR: 0.4, 95%CI: 0.2-0.95, P = 0.039). CONCLUSION: Microspheres plus gelatin embolization and main tumor size might be risk factors for post-TACE liver failure in HCC patients, while prior tumor resection could be a favorable factor reducing the risk of post-TACE liver failure.

Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B.

Objectives: We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods: A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results: We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion: Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

Firmicutes and Blautia in gut microbiota lessened in chronic liver diseases and hepatocellular carcinoma patients: a pilot study.

The gut microbiota system plays a vital role in liver diseases. This study aimed to address the diversity of gut microbiota and its correlations with clinical parameters in healthy individuals, chronic liver disease (CLD), and hepatocellular carcinoma (HCC) patients. Fecal specimens of nine healthy individuals, 11 CLD, and 21 HCC were collected. The diversity of gut microbiota was examined by PCR and Illumina MiSeq sequencing and analyzed using 16S rRNA gene sequencing database. The correlations between gut microbiota and the clinical parameters of participants were also addressed. Compared to healthy individuals, Firmicutes at a phylum level decreased in CLD and HCC patients and Proteobacteria increased (p < 0.05). The composition of Blautia on a genus level in CLD and HCC patients significantly decreased compared to healthy controls (p < 0.05). Firmicutes composition was negatively associated with age and number of males (p < 0.05) and was positively associated with monocytes, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR) levels (p < 0.05). At a genus level, Blautia composition was negatively associated with cirrhosis, age, and number of males (p < 0.01), while it was positively associated with red blood cells (RBCs), triglycerides, HDL-C, and lymphocyte levels (p < 0.05). Conclusively, there was a significant compositional difference in gut microbiota in CLD and HCC patients compared with healthy subjects. Firmicutes and Blautia in gut microbiota system lessened in CLD and HCC patients. Clinical biochemical parameters have an impact on the diversity of gut microbiota in liver diseases.

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis.

Background: MiRNAs are pivotal regulators involved in proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in hepatocellular carcinoma (HCC). The aim of this study was to investigate the influence of miR-139-5p and its target genes on the outcomes of HCC. Methods: Survival analysis of miR-139-5p in HCC was conducted in Kaplan-Meier plotter. Target genes of miR-139-5p were identified in TargetScan, miRTarBase and starBase. Gene Expression Omnibus (GEO) series were used for the validation of miR-139-5p target genes. Cox proportional regression model was also established. Results: In Kaplan-Meier plotter, 163 HCC patients were included. MiR-139-5p downregulation was significantly associated with unfavorable overall survival (OS) and disease-free survival (DFS) in HCC patients (all P < 0.001). MiR-139-5p was significantly downregulated in HCC tumors and human hepatoma cell lines (all P < 0.05). As a target gene of miR-139-5p, CCT5 was overexpressed in HCC tumor tissues and peripheral blood mononuclear cells (all P < 0.05). A negative correlation between CCT5 and miR-139-5p was found in TCGA dataset. CCT5 overexpression was significantly associated with worse OS in HCC patients (P < 0.001), which was validated in the GSE14520 dataset (P = 0.017). CCT5 mRNA was significantly overexpressed in HCC patients with alpha-fetoprotein (AFP) > 300 ng/ml, BCLC staging B-C, TNM staging III and main tumor size > 5 cm (all P < 0.05). According to the Cox regression model of CCT5-interacting genes, HCC patients with high risk had poor OS compared to those with low risk in the TCGA dataset (P < 0.001), with the 1-year, 3-year, and 5-year ROC curves of an area under the curve (AUC) equal to 0.704, 0.662, and 0.631, respectively. Conclusions: MiR-139-5p suppresses HCC tumor aggression and conversely correlated with CCT5. The miR-139-5p/CCT5 axis might perform crucial functions in the development of HCC.

Predictive performance of eLIFT for liver inflammation and fibrosis in chronic liver diseases.

Objective: The easy liver fibrosis test (eLIFT) is a novel predictor of liver fibrosis in chronic liver disease (CLD). This study aimed to evaluate the predictive value of the eLIFT for liver inflammation and fibrosis in CLD patients. Methods: We enrolled 1125 patients with CLD who underwent liver biopsy. The predictive accuracy for liver inflammation and fibrosis of the eLIFT was assessed and compared to that of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 score (FIB-4), and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) by ROC (Receiver Operating Characteristic) analysis and decision curve analysis (DCA). Results: The areas under the ROC curves (AUROCs) of the eLIFT for assessing liver inflammation G ≥ 2 and G ≥ 3 were 0.77 (0.75-0.80) and 0.81 (0.79-0.84), with cut-offs of 8.0 and 11.0, respectively. The AUROCs of the eLIFT for predicting fibrosis stages S ≥ 2 and S4 were 0.72 (0.70-0.76) and 0.76 (0.72-0.80), with cut-offs of 9.0 and 10.0, respectively. In discriminating G≥2 inflammation, the AUROC of the eLIFT was better than that of the FIB-4, with no difference compared with the GPR, but lower than that of the APRI. When discriminating G≥3 inflammation, the AUROC of the eLIFT was comparable to that of the APRI and GPR but superior to that of the FIB-4. There were no significant differences between the four indexes for predicting S≥2 and S4. Conclusion: The eLIFT is a potentially useful noninvasive predictor of liver inflammation and fibrosis in patients with CLD.

HMGCS2 in metabolic pathways was associated with overall survival in hepatocellular carcinoma: A LASSO-derived study.

This integrated bioinformatic study aimed to investigate potential prognostic candidates in hepatocellular carcinoma (HCC). In the GSE14520, GSE101685, and The Cancer Genome Atlas (TCGA) datasets, differentially expressed genes (DEGs) were identified and functional pathways of common DEGs were enriched. The least absolute shrinkage and selection operator (LASSO) model was used to screen the potential parameters associated with overall survival (OS) in HCC patients. Metabolic pathways were the most significantly enriched functional pathways of common DEGs in these three datasets. After LASSO model analysis, HMGCS2, UGP2, BCLC staging and TNM staging were screened as potential prognostic candidates for OS in HCC patients in GSE14520. HMGCS2 in the metabolic pathway was significantly downregulated in tumor tissues and peripheral blood mononuclear cells in HCC patients (all p < 0.05). Cox regression model indicated that HMGCS2 might be associate with OS in HCC patients in GSE14520 and in the TCGA (p = 0.029 and p = 0.05, respectively). Kaplan-Meier analysis demonstrated that HMGCS2 downregulation in tumors contributed to an unfavorable OS in HCC patients, both in GSE14520 and in the TCGA (p = 0.0001 and p = 0.0002, respectively). Additionally, HMGCS2 was significantly downregulated in HCC patients with high alpha-fetoprotein (AFP), main tumor size >5 cm, multinodular, advanced tumor staging including BCLC, TNM and CLIP (all p < 0.05). HMGCS2 was involved in metabolic pathways, and downregulated HMGCS2 in tumors was associated with unfavorable OS in HCC patients.

Absent in melanoma 1-like (AIM1L) serves as a novel candidate for overall survival in hepatocellular carcinoma.

Identifying biomarkers for hepatocellular carcinoma (HCC) survival is of great importance for the early detection, monitoring, and predicting for prognosis. This study aimed to investigate the candidate biomarkers for predicting overall survival (OS) in HCC patients. Using RTCGAToolbox, top 50 upregulated differential expressed genes (DEGs) were identified. The least absolute shrinkage and selection operator (LASSO) and Cox models were used to select powerful candidate genes, and log rank method was used to address the survivor functions of potential biomarkers. Selected by LASSO model, ANLN, TTK, AIM1L and person neoplasm cancer status might be candidate parameters associated with OS in HCC patients. After adjusting person neoplasm cancer status, ANLN and TTK levels in Cox model, AIM1L was identified as a risk factor for predicting OS in HCC patients (HR = 1.5, P = 0.037). Validated in The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) series, AIM1L was significantly overexpressed in tumor tissues compared to nontumor tissues (all P < 0.0001). HCC patients with high AIM1L in tumor tissues had significantly unfavorable OS compared to those with low AIM1L in TCGA, ICGC, Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter datasets (all P < 0.05). Conclusively, AIM1L is upregulated in tumor samples and serves as a novel candidate for predicting unfavorable OS in HCC patients.

A Bioinformatic Analysis of Correlations between Polymeric Immunoglobulin Receptor (PIGR) and Liver Fibrosis Progression.

OBJECTIVE: This study is aimed at investigating the enriched functions of polymeric immunoglobulin receptor (PIGR) and its correlations with liver fibrosis stage. METHODS: PIGR mRNA expression in normal liver, liver fibrosis, hepatic stellate cells (HSCs), and hepatitis virus infection samples was calculated in Gene Expression Omnibus (GEO) and Oncomine databases. Enrichment analysis of PIGR-related genes was conducted in Metascape and Gene Set Enrichment Analysis (GSEA). Logistic model and ROC curve were performed to evaluate the correlations between pIgR and liver fibrosis. RESULTS: PIGR mRNA was upregulated in advanced liver fibrosis, cirrhosis compared to normal liver (all p < 0.05). PIGR mRNA was also overexpressed in activated HSCs compared to senescent HSCs, liver stem/progenitor cells, and reverted HSCs (all p < 0.05). Enrichment analysis revealed that PIGR-related genes involved in the defense response to virus and interferon (IFN) signaling. In GEO series, PIGR mRNA was also upregulated by hepatitis virus B, C, D, and E infection (all p < 0.05). After adjusting age and gender, multivariate logistic regression models revealed that high PIGR in the liver was a risk factor for liver fibrosis (OR = 82.2, p < 0.001). The area under curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of PIGR for liver fibrosis stage >2 were 0.84, 0.86, 0.7, 0.61, and 0.90. CONCLUSION: PIGR was correlated with liver fibrosis and might involve in hepatitis virus infection and HSC transdifferentiation.

Predictive Performances of Blood Parameter Ratios for Liver Inflammation and Advanced Liver Fibrosis in Chronic Hepatitis B Infection.

OBJECTIVE: Blood parameter ratios, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), have been reported that they are correlated to the progression of liver disease. This study is aimed at evaluating the predictive value of PLR, NLR, and MLR for liver inflammation and fibrosis in patients with chronic hepatitis B (CHB). METHODS: We recruited 457 patients with CHB who underwent a liver biopsy and routine laboratory tests. Liver histology was assessed according to the Scheuer scoring system. The predictive accuracy for liver inflammation and fibrosis was assessed by receiver operating characteristics (ROC) analysis. RESULTS: PLR and NLR presented significantly reverse correlation to liver inflammation and fibrosis. However, these correlations were not observed for MLR and liver histology. The AUROCs of PLR for assessing G2-3 and G3 were 0.676 and 0.705 with cutoffs 74.27 and 68.75, respectively. The AUROCs of NLR in predicting inflammatory scores G2-3 and G3 were 0.616 and 0.569 with cutoffs 1.36 and 1.85, respectively. The AUROCs of PLR for evaluating fibrosis stages S3-4 and S4 were 0.723 and 0.757 with cutoffs 79.67 and 74.27, respectively. The AUROCs of NLR for evaluating fibrosis stages S3-4 and S4 were 0.590 with cutoff 1.14. CONCLUSION: Although PLR has similar predictive power of progressive liver fibrosis compared with APRI, FIB-4, and GPR in CHB patients, it has the advantage of less cost and easy application with the potential to be widely used in clinical practice.

Roles of APOBEC3 in hepatitis B virus (HBV) infection and hepatocarcinogenesis.

APOBEC3 (A3) cytidine deaminases inhibit hepatitis B virus (HBV) infection and play vital roles in maintaining a variety of biochemical processes, including the regulation of protein expression and innate immunity. Emerging evidence indicates that the deaminated deoxycytidine biochemical activity of A3 proteins in single-stranded DNA makes them a double-edged sword. These enzymes can cause cellular genetic mutations at replication forks or within transcription bubbles, depending on the physiological state of the cell and the phase of the cell cycle. Under pathological conditions, aberrant expression of A3 genes with improper deaminase activity regulation may threaten genomic stability and eventually lead to cancer development. This review attempted to summarize the antiviral activities and underlying mechanisms of A3 editing enzymes in HBV infections. Moreover, the correlations between A3 genes and hepatocarcinogenesis were also elucidated.

Nomogram for predicting advanced liver fibrosis and cirrhosis in patients with chronic liver disease.

BACKGROUND: We aimed to formulate a novel predictive nomogram to discriminate liver fibrosis stage in patients with chronic liver disease. METHODS: Nomograms were established based on the results of multivariate analysis. The predictive accuracy of the nomograms was assessed by ROC analysis and calibration. Decision curve analysis (DCA) was used to determine the clinical benefit of the nomograms. RESULTS: INR, platelets, and N-terminal propeptide type III collagen (PIIINP) were independent predictors for advanced liver fibrosis (≥ S3) and cirrhosis (S4) in patients with chronic liver disease in the training cohort. In the training set, the areas under the ROCs (AUROCs) of nomogram S3S4, APRI, FIB-4, and GPR for stage ≥ S3 were 0.83, 0.71, 0.68, and 0.74, respectively; the AUROCs of nomogram S4, APRI, FIB-4, and GPR for stage S4 were 0.88, 0.74, 0.78, and 0.79, respectively. The calibrations showed optimal agreement between the prediction by the established nomograms and actual observation. In the validation set, the AUROCs of nomogram S3S4, APRI, FIB-4, and GPR for stage ≥ S3 were 0.86, 0.79, 0.78, and 0.81, respectively; the AUROCs of nomogram S4, APRI, FIB-4, and GPR for stage S4 were 0.88, 0.77, 0.81, and 0.83, respectively. Furthermore, the decision curve analysis suggested that the nomograms represent better clinical benefits in both independent cohorts than APRI, FIB-4, and GPR. CONCLUSION: The constructed nomograms could be a superior tool for discriminating advanced fibrosis and cirrhosis in chronic liver disease.

C8B in Complement and Coagulation Cascades Signaling Pathway is a predictor for Survival in HBV-Related Hepatocellular Carcinoma Patients.

OBJECTIVE: The role of the complement and coagulation cascades signaling pathway in the pathogenesis of cancers remains uncertain. This study aimed to investigate the associations between enriched differentially expressed genes (DEGs) in this pathway and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Clinical and gene expression data of the Gene Expression Omnibus (GEO) series profile GSE14520 were downloaded. The "Limma" package was used to screen the DEGs and the "clusterProfiler" package was used to identify the complement and coagulation cascades pathway and enriched significant genes. Cox regression analysis, the Kaplan-Meier method, and the nomogram model were used to address the correlations between significantly enriched DEGs in the complement and coagulation cascades pathway and HCC survival. RESULTS: A total of 220 HBV-related HCC patients were enrolled in this study. The complement and coagulation cascades pathway was significantly enriched by 37 DEGs (p-value < 0.05 and adjusted p-value < 0.05). Complement 8 beta chain (C8B) expression levels had protective effects on overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. High levels of C8B contributed to favorable OS and RFS in this population (both p < 0.01), even after adjustment of clinicopathological characteristics including tumor node metastasis (TNM) staging, Barcelona Clinic liver cancer (BCLC) staging, gender, and fibrinogen beta chain (FGB) expression (all p < 0.05). CONCLUSION: C8B in the complement and coagulation cascades signaling pathway serves as a predictive candidate for survival in HBV-related HCC patients.

INR-to-platelet ratio (INPR) as a novel noninvasive index for predicting liver fibrosis in chronic hepatitis B.

Objective: We aimed to investigate whether a novel noninvasive index, i.e., the international normalized ratio-to-platelet ratio (INPR), was a variable in determining liver fibrosis stage in patients with chronic hepatitis B (CHB). Methods: A total of 543 treatment-naïve CHB patients were retrospectively enrolled. Liver histology was assessed according to the Metavir scoring scheme. All common demographic and clinical parameters were analyzed. Results: Based on routine clinical parameters (age, sex, HBeAg status, HBV DNA, hematological parameters, coagulation index, and liver biochemical indicators), a novel index, i.e., the INR-to-platelet ratio (INPR), was developed to magnify the unfavorable effects of liver fibrosis on INR and platelets. The AUCs of INPR for predicting significant fibrosis, advanced fibrosis, and cirrhosis were 0.74, 0.76 and 0.86, respectively. Compared with APRI, FIB-4, and GPR, the INPR had comparable predictive efficacy for significant fibrosis and better predictive performance for advanced fibrosis and cirrhosis. Conclusion: INPR could be an accurate, easily calculated and inexpensive index to assess liver fibrosis in patients with CHB. Further studies are needed to verify this indicator and compare it with other noninvasive methods for predicting liver fibrosis in CHB patients.

Identification of parameters in routine blood and coagulation tests related to the severity of COVID-19.

Objective: This study aimed to identify the predictive value of simple markers in routine blood and coagulation tests for the severity of coronavirus disease 2019 (COVID-19). Methods: A total of 311 consecutive COVID-19 patients, including 281 patients with mild/moderate COVID-19 and 30 patients with severe/life-threatening COVID-19, were retrospectively enrolled. Logistic modeling and ROC curve analyses were used to assess the indexes for identifying disease severity. Results: Lymphocyte and eosinophil counts of COVID-19 patients in the severe/life-threatening group were significantly lower than those of patients in the mild/moderate group (P < 0.001). Coagulation parameters, high-sensitivity C-reactive protein (hsCRP) levels and procalcitonin levels were higher in the severe/life-threatening group compared with the mild/moderate group (all P < 0.05). Univariate and multivariate logistic models revealed that hsCRP and fibrinogen degradation products (FDPs) were predictors of severe COVID-19 (OR = 1.072, P = 0.036; and OR = 1.831, P = 0.036, respectively). The AUROCs of hsCRP and FDP for predicting severe/life-threatening COVID-19 were 0.850 and 0.766, respectively. The optimal cutoffs of hsCRP and FDP for the severe/life-threatening type of COVID-19 were 22.41 mg/L and 0.95 µg/ml, respectively. Conclusion: Serum CRP and FDP levels are positively related to the severity of COVID-19. This finding indicates that CRP and FDP levels may potentially be used as early predictors for severe illness and help physicians triage numerous patients in a short time.

Polymeric immunoglobulin receptor (PIGR) exerts oncogenic functions via activating ribosome pathway in hepatocellular carcinoma.

Objective: This report aimed to investigate the potential mechanism of polymeric immunoglobulin receptor (PIGR) in promoting cancer development in hepatocellular carcinoma (HCC). Methods: PIGR expression was investigated in Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) databases. Relationships between PIGR and HCC survival and clinico-pathological features were conducted in TCGA. RNAseq of PIGR overexpression and knockdown samples in Bel-7404 cells were performed for identifying potential mechanisms. Results: PIGR was significantly overexpressed in tumors compared to nontumors and in HCC serum peripheral blood mononuclear cells (PBMC) than in healthy individuals (all p < 0.05). In TCGA, PIGR was highly altered in 14% HCC patients. PIGR upregulation was significantly associated with poor disease-free survival (p < 0.05). More patients recurred/progressed in PIGR altered group compared to unaltered group (p < 0.01). PIGR was significantly higher in HCC patients with incomplete cirrhosis (p < 0.001) and established cirrhosis (p < 0.05). Fewer patients had N0 lymph node stage in PIGR altered group than those in the unaltered group (p < 0.05). PIGR RNAseq revealed that ribosome signaling was the common pathway in PIGR overexpression and PIGR knockdown samples. RNAseq analysis indicated that RPL10, RPL10A, RPL12, RPL19, RPL36, RPL38, RPL41, RPL6, RPL8, RPS12, RPS14, RPS15A, RPS2, RPS27A and RPSA were significantly upregulated in PIGR overexpression group and downregulated in PIGR underexpression group (all p < 0.05). Conclusions: Aberrant PIGR was associated with HCC recurrence, and PIGR stimulated ribosome pathway might be a potential mechanism.

MRPL27 contributes to unfavorable overall survival and disease-free survival from cholangiocarcinoma patients.

Objective: This study aimed to investigate the roles of MRPL27 in survival from cholangiocarcinoma patients in The Cancer Genome Atlas (TCGA) database. Methods: In TCGA-CHOL profile, MRPL27 gene expression and clinical data were obtained. Cox regression models were used to evaluate the potential links between MRPL27 and cholangiocarcinoma survival. Enrichment analysis of MRPL27 was conducted in Metascape and Gene Set Enrichment Analysis (GSEA) databases. Results: 36 cholangiocarcinoma patients were included in this analysis. MRPL27 mRNA was significantly upregulated in tumor tissues in cholangiocarcinoma patients including intrahepatic, distal and hilar/perihilar cholangiocarcinoma cases (all p < 0.01). Cholangiocarcinoma patients with high MRPL27 had worse overall survival (OS) and disease-free survival (DFS) compared to those with low MRPL27 (all p < 0.05). Univariate and multivariate Cox models indicated that MRPL27 should be a risk factor for the OS and DFS in cholangiocarcinoma patients (both p < 0.01). Bioinformatic analysis revealed that MRPL27 mainly involved in the processes of mitochondrial translation elongation, respiratory electron transport, ATP synthesis, and inner mitochondrial membrane organization. No mutations of MRPL27 were screened in cholangiocarcinoma patients. Conclusion: Upregulated in tumors, MRPL27 contributes to unfavorable survival in cholangiocarcinoma patients.

Regulatory T cell and activated natural killer cell infiltration in hepatocellular carcinoma: immune cell profiling using the CIBERSORT.

BACKGROUND: Hepatocellular carcinoma (HCC) is understood to be an immunogenic tumor caused by chronic liver disease. Emerging research has indicated close interaction between various immune cells and tumor cells. Immunophenotyping, which has shown potential predictive value for the prognosis of various human malignancies, might allow responsive and non-responsive patients to be identified based on the extent and distribution of immune cell infiltration. Several novel immunotherapeutic approaches have been trialed and have shown promising efficacy. However, the efficacy of immunotherapies in HCC is limited by several factors. This study aimed to investigate tumor-infiltrating immune cells in HCC. METHODS: Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) allows immune cell profiling analysis by deconvolution of gene expression microarray data. In this study, we analyzed the proportions of immune cells in 14 paired samples of HCC tissues obtained from GSE84402 in Gene Expression Omnibus (GEO) database. RESULTS: In the 14 paired samples, HCC tissues showed significant infiltration by regulatory T cells (Tregs), activated natural killer (NK) cells, and M0 macrophages (P<0.001, P=0.007 and P=0.001, respectively), which were validated in CIBERSORT with the P value set at ≤0.05. In four paired samples identified from those selected by CIBERSORT, HCC tissues were found to have significant Treg and activated NK cell infiltration compared to non-tumor tissues (P=0.007 and P=0.015, respectively). Additionally, Pearson correlation analysis revealed Tregs to be positively correlated with activated NK cells (Correlation coefficient =0.41). CONCLUSIONS: HCC tumor tissues were markedly infiltrated by Tregs and activated NK cells, which should be considered as candidate therapeutic targets in HCC multidisciplinary treatments.