A novel liver-function-indicators-based prognosis signature for patients with hepatocellular carcinoma treated with anti-programmed cell death-1 therapy.

BACKGROUND: The liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy. METHODS: Between July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan-Meier survival curves were utilized to access the predictive performance of LFIS. RESULTS: A total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child-Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature. CONCLUSION: The LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.

Hepatic Arterial Infusion Chemotherapy vs Transcatheter Arterial Chemoembolization as Adjuvant Therapy Following Surgery for MVI-Positive Hepatocellular Carcinoma: A Multicenter Propensity Score Matching Analysis.

Background: Microvascular invasion (MVI) is a significant pathological feature in hepatocellular carcinoma (HCC), adjuvant hepatic arterial infusion chemotherapy (a-HAIC) and adjuvant transcatheter arterial chemoembolization (a-TACE), are commonly used for HCC patients with MVI. This study aims to evaluate the efficacies of two adjuvant therapies after surgical treatment for HCC, compare them, and identify the significant factors. Methods: Clinical data from two randomized controlled trials involving HCC patients with MVI after surgical treatment were retrospectively reviewed. Propensity score matching (PSM) analysis was performed to balance baseline differences between patients who received a-HAIC or a-TACE, and control groups who underwent hepatectomy alone. Disease-free survival (DFS) and overall survival (OS) rates were compared. Results: In total of 549 patients were collected from two randomized controlled trials. Using the PSM and Kaplan-Meier method, the median DFS of the a-HAIC, a-TACE, and control groups was 63.2, 21.7, and 11.2 months (P<0.05). The a-HAIC group show significantly better 1-, 3-, and 5-year OS rates compared to the a-TACE and control groups (96.3%, 80.0%, 72.8% vs 84.4%, 57.0%, 29.8% vs 84.5%, 62.8%, 53.4%, P<0.05). But the OS rates of a-TACE and control groups showed no significant difference (P=0.279). Multivariate analysis identified a-HAIC (HR=0.449, P=0.000) and a-TACE (HR=0.633, P=0.007) as independent protective factors. For OS, a-HAIC (HR=0.388, P=0.003) was identified as an independent protective factor, too. Conclusion: Compared to a-TACE and the control group, a-HAIC demonstrated greater benefits in preventing tumor recurrence and improving survival in HCC patients with MVI.

Patients with hepatocellular carcinoma extrahepatic metastases can benefit from hepatic arterial infusion chemotherapy combined with lenvatinib plus programmed Death-1 inhibitors.

BACKGROUND: Lenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. MATERIALS AND METHODS: This multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, the mOS (hazard ratio (HR)=0.384, P<0.001) and mPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05). CONCLUSION: HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.

Risk of hepatitis B virus reactivation and its effect on survival in advanced hepatocellular carcinoma patients treated with hepatic arterial infusion chemotherapy and lenvatinib plus programmed death receptor-1 inhibitors.

Background: Hepatitis B virus (HBV) reactivation is a common complication in hepatocellular carcinoma (HCC) patients treated with chemotherapy or immunotherapy. This study aimed to evaluate the risk of HBV reactivation and its effect on survival in HCC patients treated with HAIC and lenvatinib plus PD1s. Methods: We retrospectively collected the data of 213 HBV-related HCC patients who underwent HAIC and lenvatinib plus PD1s treatment between June 2019 to June 2022 at Sun Yat-sen University, China. The primary outcome was the risk of HBV reactivation. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results: Sixteen patients (7.5%) occurred HBV reactivation in our study. The incidence of HBV reactivation was 5% in patients with antiviral prophylaxis and 21.9% in patients without antiviral prophylaxis, respectively. The logistic regression model indicated that for HBV reactivation, lack of antiviral prophylaxis (P=0.003) and tumor diameter (P=0.036) were independent risk factors. The OS and PFS were significantly shorter in the HBV reactivation group than the non-reactivation group (P=0.0023 and P=0.00073, respectively). The number of AEs was more in HBV reactivation group than the non-reactivation group, especially hepatic AEs. Conclusion: HBV reactivation may occur in HCC patients treated with HAIC and lenvatinib plus PD1s. Patients with HBV reactivation had shorter survival time compared with non-reactivation. Therefore, HBV-related HCC patients should undergo antiviral therapy and HBV-DNA monitoring before and during the combination treatment.

Development of nomograms to predict recurrence after conversion hepatectomy for hepatocellular carcinoma previously treated with transarterial interventional therapy.

BACKGROUND: Lack of opportunity for radical surgery and postoperative tumor recurrence are challenges for surgeons and hepatocellular carcinoma (HCC) patients. This study aimed to develop nomograms to predict recurrence risk and recurrence-free survival (RFS) probability after conversion hepatectomy for patients previously receiving transarterial interventional therapy. METHODS: In total, 261 HCC patients who underwent conversion liver resection and previously received transarterial interventional therapy were retrospectively enrolled. Nomograms to predict recurrence risk and RFS were developed, with discriminative ability and calibration evaluated by C-statistics, calibration plots, and the Area under the Receiver Operator Characteristic (AUROC) curves. RESULTS: Univariate/multivariable logistic regression and Cox regression analyses were used to identify predictive factors for recurrence risk and RFS, respectively. The following factors were selected as predictive of recurrence: age, tumor number, microvascular invasion (MVI) grade, preoperative alpha-fetoprotein (AFP), preoperative carbohydrate antigen 19-9 (CA19-9), and Eastern Cooperative Oncology Group performance score (ECOG PS). Similarly, age, tumor number, postoperative AFP, postoperative protein induced by vitamin K absence or antagonist-II (PIVKA-II), and ECOG PS were incorporated for the prediction of RFS. The discriminative ability and calibration of the nomograms revealed good predictive ability. Calibration plots showed good agreement between the nomogram predictions of recurrence and RFS and the actual observations. CONCLUSIONS: A pair of reliable nomograms was developed to predict recurrence and RFS in HCC patients after conversion resection who previously received transarterial interventional therapy. These predictive models can be used as guidance for clinicians to help with treatment strategies.

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization, potential conversion therapies for single huge hepatocellular carcinoma: a retrospective comparison study.

BACKGROUND: The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10 cm without vascular invasion and metastasis. METHODS: From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10 cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored. RESULTS: The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS. CONCLUSIONS: HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.

Analysis of the Prognosis Prediction Ability of a Necroptosis-Related Gene Signature and its Relationship With the Hepatocellular Carcinoma Immune Microenvironment Using Bioinformatics Analysis and Experimental Validation.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant cancers and has a poor prognosis. The immune microenvironment is closely related to the drug sensitivity of a tumor. Necroptosis was reported to be a key factor for HCC. The prognostic value of necroptosis-related genes and their association with the tumor immune microenvironment are still unknown. Methods: Necroptosis-related genes that could comprise a signature for predicting the prognosis of HCC cases were identified using univariate analysis and least absolute shrinkage and selection operator Cox regression analysis. The association between this prognosis prediction signature and HCC immune microenvironment was analyzed. The immunological activities and drug sensitivities were compared between different risk score groups identified using the prognosis prediction signature. The expression levels of the five genes comprising the signature were validated using RT-qPCR. Results: A prognosis prediction signature consisting of five necroptosis-related genes was constructed and validated. Its risk score was = (0.1634 × PGAM5 expression) + (0.0134 × CXCL1 expression) - (0.1007 × ALDH2 expression) + (0.2351 × EZH2 expression) - (0.0564 × NDRG2 expression). The signature was found to be significantly associated with the infiltration of B cells, CD4+ T cells, neutrophils, macrophages, and myeloid dendritic cells into the HCC immune microenvironment. The number of infiltrating immune cells and the expression levels of immune checkpoints in the immune microenvironment of high-risk score patients were higher. Sorafenib and immune checkpoint blockade were determined to be ideally suited for treating high-risk score patients and low-risk score patients, respectively. Finally, RT-qPCR results confirmed that the expression levels of EZH2, NDRG2, and ALDH2 were significantly down-regulated in HuH7 and HepG2 cells compared to those in LO2 cells. Conclusion: The necroptosis-related gene signature developed herein can classify patients with HCC according to prognosis risk well and is associated with infiltration of immune cells into the tumor immune microenvironment.

Is the CRAFITY score a superior predictor of prognosis and adverse events in hepatocellular carcinoma patients treated with locoregional-immunotherapy?

BACKGROUND: The level of C­reactive protein (CRP) and alpha­fetoprotein (AFP) in immunotherapy (CRAFITY) score was associated with the prognosis of hepatocellular carcinoma (HCC) patients treated with immunotherapy. Based on the CRAFITY score, this study aimed to investigate the efficacy and safety of locoregional-immunotherapy for treating HCC patients. METHODS: HCC patients who received locoregional-immunotherapy were consecutively recruited at Sun Yat-sen University Cancer Center in 2019. CRAFITY 0 score was defined as the AFP level below 100 ng/ml and a CRP level of less than 1 mg/dl, CRAFITY 1 score was defined as the AFP level of at least 100 ng/ml or the CRP level of at least 1 mg/dl, and CRAFITY 2 score was defined as both the AFP level over 100 ng/ml and the CRP level of more than 1 mg/dl. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The second outcomes were tumor response rate and treatment-related adverse events (AEs). RESULTS: The median PFS for HCC patients with the CRAFITY 0 score was not estimable. The PFS was 11.0 months [95% confidence interval (CI) 7.2-14.9] and 6.0 months (95% CI 4.2-7.8) for patients with CRAFITY 1 and 2 scores, respectively, with a significant difference between the two groups (p < 0.001). HCC patients with CRAFITY 0, 1, and 2 scores had 3 years OS rates of 63.8%, 60.8%, and 32.1%, respectively, with statistical differences among the three groups (p < 0.001). Patients with the CRAFITY 2 score were more likely to experience fever than those with other scores (p < 0.05). A greater CRAFITY score was correlated with a higher incidence of grade 3 and above liver injury (p < 0.01). CONCLUSIONS: The CRAFITY score is a superior predictor of prognosis and treatment-related AEs in HCC patients treated with locoregional-immunotherapy.

Nomograms for predicting the recurrence probability and recurrence-free survival in patients with hepatocellular carcinoma after conversion hepatectomy based on hepatic arterial infusion chemotherapy: a multicenter, retrospective study.

BACKGROUND: This study aimed to establish and validate nomograms to predict the probability of recurrence and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) after conversion hepatectomy based on hepatic arterial infusion chemotherapy (HAIC). METHODS: Nomograms were constructed using data from a retrospective study of 214 consecutive patients treated with HAIC-based conversion liver resection between January 2016 and July 2020. Nomograms predicting the probability of tumor recurrence and RFS were established based on predictors selected by multivariate regression analysis. Predictive accuracy and discriminative ability of the nomogram were examined. Bootstrap method was used for internal validation. External validation was performed using cohorts ( n =128) from three other centers. RESULTS: Recurrence rates in the primary and external validation cohorts were 63.6 and 45.3%, respectively. Nomograms incorporating clinicopathological features of tumor recurrence and RFS were generated. Concordance index (C-index) scores of the nomograms for predicting recurrence probability and RFS were 0.822 (95% CI, 0.703-0.858) and 0.769 (95% CI, 0.731-0.814) in the primary cohort, and 0.802 (95% CI, 0.726-0.878) and 0.777 (95% CI, 0.719-0.835) in the external validation cohort, respectively. Calibration curves indicated good agreement between the nomograms and actual observations. Moreover, the nomograms outperformed the commonly used staging systems. Patients with low risk, stratified by the median nomogram scores had better RFS (low risk vs. high risk, 36.5 vs. 5.2 months, P <0.001). The external validation cohort supported these findings. CONCLUSIONS: The presented nomograms showed favorable accuracy for predicting recurrence probability and RFS in HCC patients treated with HAIC-based conversion hepatectomy. Identifying risk factors and estimating tumor recurrence may help clinicians in the decision-making process regarding adjuvant therapies for patients with HCC, which eventually achieves better oncological outcomes.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

A preliminary study on drug switching strategy for second-line therapy after combination treatment of tyrosine kinase inhibitors and immune checkpoint inhibitors for unresectable hepatocellular carcinoma.

Background: Combination treatment with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been widely used in patients with unresectable hepatocellular carcinoma (uHCC). As no standard guidelines exist for second-line therapy after failure of combination treatment, this study aimed to determine a better drug-switching strategy. Methods: A total of 785 patients with uHCC who initially received a combination treatment of TKIs and ICIs between January 2017 and December 2021 at our center were screened. After applying the inclusion and exclusion criteria, a total of 102 patients were included in the study. Based on drug switching strategy, patients were divided into a single drug-switching group (A group, n = 49) and a double drug-switching group (B group, n = 53). The comparative effectiveness between groups A and B was assessed based on treatment response and survival time. Second progression-free survival (SPFS) and overall survival (OS) were compared using the Kaplan-Meier method and log-rank test. Results: Compared to group B, group A had a higher overall response rate (16.3% vs. 3.8%; p = 0.0392) and disease control rate (61.2% vs. 49.1%; p = 0.238). The median SPFS in group A was longer than that in group B (5.47 vs. 3.8 months; HR = 1.70, p = 0.0176). In the second-line therapy, the inclusion of lenvatinib resulted in a better SPFS than other TKI treatments (5.53 vs. 2.83 months, p = 0.0038). Conclusion: After the failure of the combination treatment of TKIs and ICIs, single-drug switching significantly prolonged median SPFS in uHCC patients, and retaining lenvatinib resulted in the survival benefit of single-drug switching.

Nomogram Based on Inflammatory Biomarkers to Predict the Recurrence of Hepatocellular Carcinoma-A Multicentre Experience.

Purpose: Our study aimed to identify inflammatory biomarkers and develop a prediction model to stratify high-risk patients for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) recurrence after curative resection. Patients and Methods: A total of 583 eligible HBV-HCC patients with curative hepatectomy from Guangdong Provincial People's Hospital (GDPH) and Sun Ya-sen University Cancer Centre (SYSUCC) were enrolled in our study. Cox proportional hazards regression was utilized to evaluate potential risk factors for disease-free survival (RFS). The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to assess the discrimination performance. Calibration plots and decision curve analyses (DCA) were used to evaluate the calibration of the nomogram and the net benefit, respectively. Results: Based on the systemic inflammation response index (SIRI), aspartate aminotransferase to neutrophil ratio index (ANRI), China Liver Cancer (CNLC) stage and microvascular invasion, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 2-, and 3-year RFS was 0.767, 0.726, and 0.708 in the training cohort and 0.761, 0.716, and 0.715 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability. Conclusion: The novel nomogram showed a higher prognostic power for the RFS of HCC patients with curative hepatectomy than the CNLC, AJCC 8th edition and BCLC staging systems and may help oncologists identify high-risk HCC patients.

Four-gene signature predicting overall survival and immune infiltration in hepatocellular carcinoma by bioinformatics analysis with RT‒qPCR validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers, with a poor prognosis. Prognostic biomarkers for HCC patients are urgently needed. We aimed to establish a nomogram prediction system that combines a gene signature to predict HCC prognosis. METHODS: Differentially expressed genes (DEGs) were identified from publicly available Gene Expression Omnibus (GEO) datasets. The Cancer Genome Atlas (TCGA) cohort and International Cancer Genomics Consortium (ICGC) cohort were regarded as the training cohort and testing cohort, respectively. First, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) regression Cox analysis were performed to construct a predictive risk score signature. Furthermore, a nomogram system containing a risk score and other prognostic factors was developed. In addition, a correlation analysis of risk group and immune infiltration was performed. Finally, we validated the expression levels using real-time PCR. RESULTS: Ninety-five overlapping DEGs were identified from four GEO datasets, and we constructed a four-gene-based risk score predictive model (risk score = EZH2 * 0.075 + FLVCR1 * 0.086 + PTTG1 * 0.015 + TRIP13 * 0.020). Moreover, this signature was an independent prognostic factor. Next, the nomogram system containing risk score, sex and TNM stage indicated better predictive performance than independent prognostic factors alone. Moreover, this signature was significantly associated with immune cells, such as regulatory T cells, resting NK cells and M2 macrophages. Finally, RT‒PCR confirmed that the mRNA expressions of four genes were upregulated in most HCC cell lines. CONCLUSION: We developed and validated a nomogram system containing the four-gene risk score, sex, and TNM stage to predict prognosis.

Development and Validation of a Novel Nomogram for Predicting Vessels that Encapsulate Tumor Cluster in Hepatocellular Carcinoma.

BACKGROUND: Vessels that encapsulate tumor cluster (VETC) is associated with poor prognosis in hepatocellular carcinoma (HCC). Vessels that encapsulate tumor cluster estimation before initial treatment is helpful for clinical doctors. We aimed to construct a novel predictive model for VETC, using preoperatively accessible clinical parameters and imagine features. METHODS: Totally, 365 HCC patients who received curative hepatectomy in the Sun Yat-Sen University Cancer Center from 2013 to 2014 were enrolled in this study. Vessels that encapsulate tumor cluster pattern was confirmed by immunochemistry staining. 243 were randomly assigned to the training cohort while the rest was assigned to the validation cohort. Independent predictive factors for VETC estimation were determined by univariate and multivariate logistic analysis. We further constructed a predictive nomogram for VETC in HCC. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curve, and calibration curve. Besides, the decision curve was plotted to evaluate the clinical usefulness. Ultimately, Kaplan-Meier survival curves were utilized to confirm the association between the nomogram and survival. RESULTS: Immunochemistry staining revealed VETC in 87 patients (23.8%). lymphocyte to monocyte ratio (>7.75, OR = 4.06), neutrophil (>7, OR = 4.48), AST to ALT ratio (AAR > .86, OR = 2.16), ALT to lymphocyte ratio index (BLRI > 21.73, OR = 2.57), alpha-fetoprotein (OR = 1.1), and tumor diameter (OR = 2.65) were independent predictive factors. The nomogram incorporating these predictive factors performed well with an area under the curve (AUC) of .746 and .707 in training and validation cohorts, respectively. Calibration curves indicated the predicted probabilities closely corresponded with the actual VETC status. Moreover, the decision curve proved our nomogram could provide clinical benefits with patients. Finally, low probability of VETC group had significantly longer recurrence free survival (RFS) and overall survival (OS) than the high probability of the VETC group (all P < .001). CONCLUSION: A novel predictive nomogram integrating clinical indicators and image characteristics shows strong predictive VETC performance and might provide standardized net clinical benefits.

Microvascular Invasion in Hepatocellular Carcinoma: A Review of Its Definition, Clinical Significance, and Comprehensive Management.

Hepatocellular carcinoma (HCC) is one of the most common types of malignancies in the world, and most HCC patients undergoing liver resection relapse within five years. Microvascular invasion (MVI) is an independent factor for both the disease-free survival and overall survival of HCC patients. At present, the definition of MVI is still controversial, and a global consensus on how to evaluate MVI precisely is needed. Moreover, this review summarizes the current knowledge and clinical significance of MVI for HCC patients. In terms of management, antiviral therapy, wide surgical margins, and postoperative transcatheter arterial chemoembolization (TACE) could effectively reduce the incidence of MVI or improve the disease-free survival and overall survival of HCC patients with MVI. However, other perioperative management practices, such as anatomical resection, radiotherapy, targeted therapy and immune therapy, should be clarified in future investigations.

The pyroptosis-related gene signature predicts prognosis and indicates immune activity in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors with poor survival. Pyroptosis is a kind of programmed cell death that can regulate the proliferation, invasion, and metastasis of tumor cells. However, the expression levels of pyroptosis-related genes (PRGs) in HCC and their relationship with prognosis are still unclear. METHODS: Our study identified 35 PRGs through bioinformatics analysis that were differentially expressed between tumor samples and nontumor samples. According to these differentially expressed genes, HCC patients could be divided into two groups, cluster 1 and cluster 2. The least absolute shrinkage and selection operator (LASSO) Cox regression method was performed to construct a 10-gene signature that classified HCC patients in the cancer genome atlas (TCGA) database into low-risk and high-risk groups. RESULTS: The results showed that the survival rate of HCC patients in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The validation cohort, the Gene Expression Omnibus (GEO) cohort, was divided into two risk groups based on the median risk score calculated by the TCGA cohort. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group (p = 0.007). Univariate and multivariate Cox regression analyses revealed that the risk score was an independent factor in predicting OS in HCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that immune-related high-risk groups were rich in genes and had reduced immune status. CONCLUSIONS: PRGs play a significant role in tumor immunity and have the potential capability to predict the prognosis of HCC patients.

Development of a novel prognostic nomogram for the early recurrence of liver cancer after curative hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. Curative resection is an effective treatment but HCC recurrence rates remain high. This study aimed to establish a novel prognostic nomogram to assess the risk of recurrence in patients following curative resection. METHODS: A total of 410 patients undergoing HCC curative resection were recruited from the Guangdong Provincial People's Hospital (GDPH). The cohort was divided into a training group (n=291) and a validation group (n=97). The risk factors for HCC early recurrence within 1 year of curative hepatectomy were identified. Finally, a multivariate prognostic nomogram was developed and validated. RESULTS: Age, tumor number, tumor capsule, portal vein tumor thrombi, pathological grade, vascular tumor emboli, activated partial thromboplastin time (APTT), and tumor size were identified as independent prognostic risk factors for HCC early recurrence within 1 year of curative hepatectomy. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.806 [95% confidence interval (CI): 0.755 to 0.857; P<0.001], and no AUC/ROC statistical difference was detected between the training and validation sets. CONCLUSIONS: The nomogram effectively predicted postoperative HCC recurrence within 1 year after curative hepatectomy, which may be a useful tool for the postoperative treatment or follow up for HCC patients.

A Calculation Model for Cooling Rate of Aluminum Alloy Melts during Continuous Rheo-Extrusion.

The melt temperature of aluminum alloys plays a significant role in determining the microstructure characteristic during continuous rheo-extrusion. However, it is difficult to measure the actual melt temperature in the roll-shoe gap. In this work, based on the basic theory of heat transfer, a calculation model for heat transfer coefficient of cooling water/roll interface and melt/roll interface is established. In addition, the relationship between the temperature at the melt/roll interface and the velocity of cooling water is investigated. Combined with the CALPHAD calculation, the melt temperature during solidification in the continuous rheo-extrusion process is calculated. Using this model, the cooling rate of an Al-6Mg (wt.%) alloy melt prepared by continuous rheo-extrusion is estimated to be 10.3 K/s. This model used to determine the melt parameters during solidification provides a reference for optimizing the production process of continuous rheo-extrusion technology.

A Comprehensive Exploration of the lncRNA CCAT2: A Pan-Cancer Analysis Based on 33 Cancer Types and 13285 Cases.

Whether the lncRNA CCAT2 expression level affects the clinical progression and outcome of cancer patients has not yet been fully elucidated. There is still an inconsistent view regarding the correlation between CCAT2 expression and clinicopathological factors, including survival data. Besides, the regulation mechanism of CCAT2 in human cancer is still unclear. Our study analyzed a large number of publication data and TCGA databases to identify the association of CCAT2 expression with clinicopathological factors and to explore the regulatory mechanisms in human cancers. We designed a comprehensive study to determine the expression of CCAT2 in human cancer by designing a meta-analysis of 20 selected studies and the TCGA database, using StataSE 12.0 to explore the relationship between CCAT2 expression and both the prognosis and clinicopathological features of 33 cancer types and 13285 tumor patients. Moreover, we performed GO and KEGG pathway enrichment analyses on potential target genes of CCAT2 collected from GEPIA and LncRNA2Target V2.0. The level of CCAT2 expression in tumor tissues is higher than that in paired normal tissues and is significantly associated with a poor prognosis in cancer patients. Besides, overexpression of CCAT2 was significantly associated with tumor size, clinical stage, and TNM classification. Meanwhile, CCAT2 expression is the highest in stage II of human cancer, followed by stage III. Finally, 111 validated target gene symbols were identified, and GO and KEGG demonstrated that the CCAT2 validation target was significantly enriched in several pathways, including microRNAs in the cancer pathway. In summary, CCAT2 can be a potential biomarker associated with the progression and prognosis of human cancer.