BackgroundThe aim of this study was to investigate the expression and silencing of the S100A8 gene, which encodes the S100 calcium-binding protein A8 (S100A8), and apoptosis and phosphorylation of protein kinase B (Akt) in tissue samples of endometrial carcinoma and HEC-1A endometrial adenocarcinoma cells in vitro.Material/MethodsImmunohistochemistry (IHC) was used to detect expression of the S100A8 protein in 74 tissue samples of endometrial cancer and 22 normal endometrial tissue samples. A stable S100A8 gene knockdown cell line was constructed using lentiviral packing short hairpin RNA (shRNA) transfected into HEC-1A cells. S100A8 mRNA and S100A8 protein levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The effects of expression of the S100A8 gene by endometrial cancer cells was investigated by the MTT assay, cell cycle and apoptotic assays, qRT-PCR, and Western blotting.ResultsIHC showed high levels of expression of S100A8 protein in endometrial carcinoma tissues, and HEC-1A adenocarcinoma cells (in G1 and G2). Increased expression of S100A8 protein was found endometrial cancer tissues compared with normal endometrial tissues (79.7% vs. 4.5%). S100A8 gene knockdown reduced cell proliferation in the HEC-1A cells compared with control cells, induced cell apoptosis, inhibited the phosphorylation of protein kinase B (Akt), and induced the expression of pro-apoptotic genes, including the cytochrome C gene, CYCS, BAD, BAX, FOXO1, FOXO3, CASP9, and CASP3.ConclusionsIn endometrial carcinoma cells, down-regulation of the S100A8 gene induced cell apoptosis via inhibition of the phosphorylated or active form of protein kinase B (Akt).

The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.

Background: This study aimed to compare the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with antiangiogenic agents in patients with unresectable hepatocellular carcinoma (HCC).Methods: We conducted a systematic literature search of articles published between the establishment of the database and February 2022. Data were extracted and analyzed using STATA 14.0.Results: Six randomized controlled trials (RCTs) (980 patients for combination therapy and 565 patients for monotherapy) and 5 single-arm studies (246 patients for ICIs combination therapy) were enrolled. The objective response rate (ORR) and disease control rate (DCR) were 26% and 70%, respectively, after ICIs combination therapy. Compared with monotherapy in RCTs, ICIs combination therapy resulted in higher progression-free survival (PFS) and overall survival (OS), but also increased the incidence of adverse events (AEs). Increased incidences of fatigue, hypertension, hyperbilirubinemia, proteinuria, and nausea were more common after ICIs combination therapy. Conclusion:The analysis results reveal that ICI-combined anti-angiogenesis therapy has higher efficacy than either ICIs or antiangiogenesis options for unresectable HCC, but it is necessary to manage the AEs.Abbreviations: AE = adverse event, DCR = disease control rate, HCC = hepatocellular carcinoma, HR = hazard ratio, ICI = immune checkpoint inhibitor, ORR = objective response rate, OS = overall survival, PD-1 = programmed cell death protein-1, PD-L1 = programmed death ligand-1, PFS = progression-free survival, RCT = randomized controlled trial, RD = risk difference, RR = risk ratio, TRAE = treatment-related AE, VEGF = vascular endothelial growth factor.

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