PVR-A Prognostic Biomarker Correlated with Immune Cell Infiltration in Hepatocellular Carcinoma.

The poliovirus receptor (PVR) is a member of the immunoglobulin superfamily (Ig SF) and is essential for the promotion of cancer cell proliferation and invasion. However, the correlation between PVR expression and prognosis as well as immune infiltration in hepatocellular carcinoma (HCC) remains unclear. The expression level of PVR was quantified using the Tumor and Tumor Immunity Evaluation Resource (TIMER) and Sangerbox. The Gene Expression Omnibus (GEO) database was used to validate the PVR expression. The receiver operating characteristic (ROC) curve was used to evaluate the feasibility of using PVR as a differentiating factor according to the area under curve (AUC) score. A PVR binding protein network was built using the STRING tool. An enrichment analysis using the R package clusterProfiler was used to explore the potential function of PVR. Immune infiltration analysis was calculated with ESTIMATE algorithms. We also assessed the correlation between PVR expression and immune infiltration by the single-sample Gene Set Enrichment Analysis (ssGSEA) method from the R package GSVA and TIMER database. The results showed that PVR was commonly overexpressed in multiple types of tumors including HCC. The data of GSE64041 confirmed the same result. The ROC curve suggested that PVR could be a potential diagnostic biomarker. Additionally, high mRNA expression of PVR in HCC was significantly correlated with poor overall survival (OS) and relapse free survival (RFS). Results also indicated correlations between PVR mRNA expression with the level of infiltration immune cells including B cells, CD8+ T cells, cytotoxic cells, DCs, CD56dim NK cells, pDCs, and Th2 cells. Furthermore, the PVR level was significantly correlated with immune markers for immunosuppressive cells in HCC. In conclusion, PVR might be an important regulator of tumor immune cell infiltration and a valuable prognostic biomarker in HCC. However, additional work is needed to fully elucidate the underlying mechanisms.

Prognostic significance of preoperative systemic immune-inflammation index in combined hepatocellular-cholangiocarcinoma.

BACKGROUND: Inflammation-based prognostic scores have been increasingly used for prognosis prediction in malignant tumors. However, no existing study has comprehensively evaluated these scores in combined hepatocellular-cholangiocarcinoma (cHCC-CCA). OBJECTIVE: This study aimed to identify a robust inflammation-based prognostic predictor for cHCC-CCA. METHODS: We retrospectively analyzed 220 patients pathologically confirmed as Allen type C cHCC-CCA. The univariate and multivariate analyses were used to explore the associations between clinical variables and prognosis of cHCC-CCA. The propensity score-matching (PSM) was performed to reduce the effects of potential cofounders and selection bias. Finally, the predictive values of different inflammation-based indices were compared by using time-dependent receiver operating characteristic (ROC) curves. RESULTS: The systemic immune-inflammation index (SII) and aspartate aminotransferase to platelet ratio index (APRI) were identified as independent prognostic predictors in multivariate analysis. After PSM, the survival differences were still significant between SII-high group and SII-low group (P= 0.016 for RFS and P= 0.001 for OS). Further ROC analysis showed that the SII harbored the largest 1-, 3- and 5-year area under the curves (AUC) values as compared with other scores. CONCLUSIONS: The SII may serve as a preferable predictor of both recurrence-free survival (RFS) and overall survival (OS) in patients with cHCC-CCA.

Albumin-to-alkaline phosphatase ratio as a predictor of tumor recurrence and prognosis in patients with early-stage hepatocellular carcinoma undergoing radiofrequency ablation as initial therapy.

OBJECTIVE: Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy. METHODS: This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated. RESULTS: Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65-0.79) in the training cohort and 0.72 (95% CI: 0.63-0.81) in the validation cohort, which significantly outperformed other existing staging systems. CONCLUSIONS: AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.

A new substage classification strategy for Barcelona Clinic Liver Cancer stage B patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma are a heterogeneous population, and the classifications available could not predict the prognosis accurately. Herein, we proposed a new substage classification method, Scoring Method for Intermediate Stage, for precise classification and clinical guidance in hepatocellular carcinoma patients within Barcelona Clinic Liver Cancer stage B. METHODS: A total of 1026 stage B patients of hepatocellular carcinoma who underwent transcatheter arterial chemoembolization as a first-line treatment in Liver Cancer Institute, Zhongshan Hospital, Fudan University were retrospectively enrolled. The prognostic evaluation ability of the new substage classification criteria was analyzed, in comparison with the existing substage classification criteria. RESULTS: Using Scoring Method for Intermediate Stage, 1026 stage B patients were subclassified into three subgroups, based on Child-Pugh score and up-to-7 grade, as B1 (scoring 2), B2 (scoring 3 or 4), and B3 (scoring 5 or 6). The median survival time of the three substages was 29 (95% confidence interval [CI]: 25-36), 19 (95% CI: 16-21), and 10 (95% CI: 8-12) months, respectively. More favorable discrimination efficacy was identified by the new criteria in comparison with the existing substage classification criteria, including Bolondi, Kinki, MICAN, and Kim's criteria. Moreover, multivariate analyses indicated that the novel classification was highly associated with prognosis (Hazard ratio(s) = 1.63, 95% CI: 1.43-1.86, P < 0.001). CONCLUSIONS: Scoring Method for Intermediate Stage demonstrates satisfying capacity in classifying patients with stage B hepatocellular carcinoma and predicting prognosis.