Identification of a bile acid and bile salt metabolism-related lncRNA signature for predicting prognosis and treatment response in hepatocellular carcinoma.

Bile acids and salts have been shown to play a role in liver carcinogenesis through DNA damage, inflammation, and tumor proliferation. However, the correlation between bile acid metabolism and hepatocellular carcinoma (HCC) prognosis remains unclear. This study aimed to identify a predictive signature of bile acid and bile salt metabolism-related long non-coding RNAs (lncRNAs) for HCC prognosis and treatment response. The study used HCC RNA-sequencing data and corresponding clinical and prognostic data from The Cancer Genome Atlas. A prognostic model consisting of five bile acid and bile salt metabolism-related lncRNAs was developed and evaluated in a training set, a validation set and an external set. The model demonstrated good performance in predicting HCC prognosis and was shown to be an independent biomarker for prognosis. Additionally, our study revealed a significant association between the signature and immune cell infiltration, as well as its predictive value for therapeutic responses to both immunotherapy and chemotherapy. Furthermore, three LncRNAs (LUCAT1, AL031985.3 and AC015908.3) expression levels in our signature were validated through qRT-PCR in a cohort of 50 pairs of HCC patient tumor samples and corresponding adjacent non-tumor samples, along with 10 samples of normal liver tissue adjacent to benign lesions. These findings suggest that this novel bile acid and bile salt metabolism-related lncRNA signature can independently predict the prognosis of patients with HCC and may be utilized as a potential predictor of response to treatment in this setting.

Development and validation of lymph node ratio-based nomograms for primary duodenal adenocarcinoma after surgery.

Background: The prediction models for primary duodenal adenocarcinoma (PDA) are deficient. This study aimed to determine the predictive value of the lymph node ratio (LNR) in PDA patients and to establish and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) for PDAs after surgical resection. Methods: We extracted the demographics and clinicopathological information of PDA patients between 2004 and 2018 from the Surveillance, Epidemiology and End Results database. After screening cases, we randomly divided the enrolled patients into training and validation groups. X-tile software was used to obtain the best cut-off value for the LNR. Univariate and multivariate Cox analyses were used in the training group to screen out significant variables to develop nomograms. The predictive accuracy of the nomograms was evaluated by the concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). Finally, four risk groups were created based on quartiles of the model scores. Results: A total of 978 patients were included in this study. The best cut-off value for the LNR was 0.47. LNR was a negative predictive factor for both OS and CSS. Age, sex, grade, chemotherapy and LNR were used to construct the OS nomogram, while age, grade, chemotherapy, the number of lymph nodes removed and LNR were incorporated into the CSS nomogram. The C-index, calibration curves and AUC of the training and validation sets revealed their good predictability. DCA showed that the predictive value of the nomograms was superior to that of the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition). In addition, risk stratification demonstrated that patients with higher risk correlated with poor survival. Conclusions: The LNR was an adverse prognostic determinant for PDAs. The nomograms provided an accurate and applicable tool to evaluate the prognosis of PDA patients after surgery.

Prognostic Nomogram Based on the Metastatic Lymph Node Ratio for T1-4N0-1M0 Pancreatic Neuroendocrine Tumors After Surgery.

Purpose: This study aimed to investigate the prognostic significance of the metastatic lymph node ratio (LNR) in patients with pancreatic neuroendocrine tumors (pNETs) and to develop and validate nomograms to predict 5-, 7-, and 10-year overall survival (OS) and cancer-specific survival (CSS) rates for pNETs after surgical resection. Methods: The demographics and clinicopathological information of T1-4N0-1M0 pNET patients between 2004 and 2018 were extracted from the Surveillance, Epidemiology and End Results database. X-tile software was used to determine the best cutoff value for the LNR. Patients were randomly divided into the training and the validation groups. A Cox regression model was used in the training group to obtain independent prognostic factors to develop nomograms for predicting OS and CSS. The concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to assess the nomograms. Patients were divided into four groups according to the model scores, and their survival curves were generated by the Kaplan-Meier method. Results: A total of 806 patients were included in this study. The best cutoff value for the LNR was 0.16. The LNR was negatively correlated with both OS and CSS. Age, sex, marital status, primary site, grade, the LNR and radiotherapy were used to construct OS and CSS nomograms. In the training group, the C-index was 0.771 for OS and 0.778 for CSS. In the validation group, the C-index was 0.737 for OS and 0.727 for CSS. The calibration curves and AUC also indicated their good predictability. DCA demonstrated that the nomograms displayed better performance than the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition). Risk stratification indicated that patients with higher risk had a worse prognosis. Conclusions: The LNR is an independent negative prognostic factor for pNETs. The nomograms we built can accurately predict long-term survival for pNETs after surgery.

Survival analysis following microwave ablation or surgical resection in patients with hepatocellular carcinoma conforming to the Milan criteria.

The aim of the present study was to compare the efficacy of microwave ablation (MWA) and surgical resection (RES) for the treatment of hepatocellular carcinoma (HCC) conforming to the Milan criteria and the associated short- and long-term survival rates. The baseline characteristics were obtained from 231 patients with HCC who met the Milan criteria. To compare the mortality rates between groups, survival analysis was conducted using the Kaplan-Meier method and the log-rank test. The factors associated with the survival rate were analyzed using Cox proportional hazard models. A total of 115 patients underwent RES, and 116 were treated with MWA. No significant differences were observed in the 1-, 3- and 5-year OS rates and the 1-year DFS rate between the two groups. The 7- and 10-year OS rates and the 3-, 5-, 7- and 10-year DFS rates of the RES group were significantly higher compared with those in the MWA group (P=0.004, P=0.002, P=0.003 and P=0.002, respectively). In addition, no marked differences were observed in the OS and DFS rates between the two groups of patients with solitary HCC lesions ≤3 cm (P=0.066 and P=0.056) and in the OS of those with solitary lesions of 3-5 cm (P=0.133); however the DFS of patients with single 3-5 cm HCC lesions in the RES group was notably higher compared with the MWA group (P=0.027). The Cox proportional hazard model revealed that age, hepatitis B and C virus infection, tumor size, number, platelet count and the type of treatment intervention were risk factors affecting the survival and recurrence in patients with HCC. These results suggested that RES may provide superior survival benefits compared with MWA for patients with HCC who meet the Milan criteria.

Interleukin 22 is related to development and poor prognosis of hepatocellular carcinoma.

BACKGROUND AND AIMS: Immune response against hepatitis B virus (HBV) infection is an important risk factor for the development of hepatocellular carcinoma (HCC). Studies have reported that interleukin 22 (IL-22) exhibits both protective and pathological properties in liver diseases. Our aim was to explore the importance of IL-22 in the development of HCC, and to characterize the relationship between IL-22 levels and the prognosis of HCC. METHODS: Totally, 136 liver biopsy specimens from 46 patients with chronic hepatitis B (CHB), 37 with atypical hyperplasia (AH), 53 with HCC, patient-matched tumors and peritumoral surgical specimens from 56 HCC patients included in the study. The expression of IL-22 and CD8 was evaluated by immunochemistry. Corresponding serum samples were collected from 30 CHB, 30 AH, and 30 HCC patients. IL-22 expression was determined by an enzyme linked immunosorbent assay. RESULTS: Liver-infiltrating IL-22+ cells increased in a stepwise manner from CHB to AH and HCC (CHB vs. AH, P=0.002; AH vs. HCC, P=0.010), whereas a decreasing trend was observed for CD8+ T cells (CHB vs. AH, P=0.031; AH vs. HCC, P=0.652). Serum IL-22 levels also increased from CHB to AH and HCC (CHB vs. AH, P=0.024; AH vs. HCC, P=0.026). Tumor-infiltrating IL-22+ cells and serum IL-22 were associated with histologic grade (P=0.024 and P=0.033). Additionally, CD8+ T cells correlated with tumor size (P=0.032). Furthermore, the high intratumoral IL-22+ cell group and high serum IL-22 group showed lower overall survival (OS; P=0.001, P=0.017) and disease-free survival (DFS; P=0.005, P<0.001). Multivariate analysis revealed that intratumoral IL-22+ cells and serum IL-22 levels were independent prognostic factors for both OS and DFS. CONCLUSIONS: These findings indicate that IL-22 promotes the progression of HCC in CHB patients. High tumor-infiltrating IL-22+ cells and serum IL-22 levels are thought to be unfavorable prognostic indicators for HCC.

The Diagnostic Value of Chemokine/Chemokine Receptor Pairs in Hepatocellular Carcinoma and Colorectal Liver Metastasis.

Chemokines and their receptors have been proposed to play important roles in tumor progression and metastasis. To investigate their roles in the progression of primary and metastatic malignant liver tumors and their prognosis, we compared expression profiles of CXCL12/CXCR4, CCL20/CCR6, and CCL21/CCR7 in hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM). Immunohistochemistry was used to analyze the expression levels of the chemokine/chemokine receptor pairs in 29 HCC and 11 CRLM specimens and adjacent non-cancerous tissues, and correlations with clinicopathological variables and overall survival were determined. CCL20/CCR6 expression was higher in HCC than in adjacent non-cancerous tissues. High CCR6 expression in HCC was negatively associated with 5-year survival rate and was an independent prognostic factor for overall survival of HCC patients, whereas differences were not observed between CRLM and adjacent tissues. Furthermore, significantly higher expression of CCL21/CCR7 was found in CRLM than in HCC. In summary, the CCL20/CCR6 axis was elevated in HCC but not in CRLM, whereas the CCL21/CCR7 axis was elevated in CRLM but not in HCC.

Comparison of microwave ablation and surgical resection for treatment of hepatocellular carcinomas conforming to Milan criteria.

BACKGROUND AND AIM: To compare the efficacy of microwave ablation (MWA) and surgical resection (RES) in the treatment of hepatocellular carcinoma (HCC) conforming to Milan criteria. METHODS: Two hundred twenty-four patients met the inclusion criteria and were enrolled in the study. One hundred and seventeen patients received MWA, and 107 patients underwent RES. The primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: The 1-, 3-, and 5-year OS rates were 94%, 70%, 52% for the MWA group and 94%, 72%, 60% for the RES group (P = 0.513). The corresponding DFS rates for the two groups were 77%, 38%, 18% and 85%, 57%, 31% (P = 0.005). In subgroup analyses of patients with solitary HCC ≤ 3 cm, there were no significant differences in OS rates and DFS rates between the two groups (P = 0.577 and P = 0.140). For patients with solitary HCC 3 to 5 cm, there was no significant differences in OS rates between the two groups (P = 0.820), the DFS rates was significantly higher in the RES group than in the MWA group (P = 0.014). CONCLUSIONS: MWA results in lower DFS rates than RES for HCC conforming to Milan criteria. However, the OS rates are comparable between the two therapies. For solitary HCC ≤ 3 cm, MWA is as effective as RES.