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Background The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC. Results Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC.

AimsThe probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma as this represents a mixed category of benign and malignant cases. It would be beneficial to be able to predict malignancy based on specific cytological features in C3 aspirates.MethodsA comprehensive panel of cytological features (including quantitative, cytomorphological and background features) in a large cohort of C3 breast aspirates with subsequent histological excisions was evaluated to identify relevant morphological criteria predicting the risk of subsequent malignancy.ResultsA total of 229 C3 specimens with histological follow-up were included. Malignant outcome was found in 30.1% of specimens and the majority were invasive cancers. Features that showed a significant association with malignant outcome included older age (p=0.001), lower percentage of epithelial cell clusters and high percentage of single cells (p=0.002), cribriform architecture in cell clusters (p=0.034), presence of intracellular mucin (p=0.027), increased cell clusters without myoepithelial cells (p=0.048), diminished fibromyxoid stromal fragments (p=0.001), reduced bipolar nuclei (p=0.021) and the presence of necrosis (p=0.023). Except for the percentages of single cells and cell clusters without myoepithelial cells, all other features were shown to be independent risk predictors in multivariate analysis.ConclusionsC3 aspirates were associated with a significant probability of histological malignancy. Certain quantitative, cytomorphological and background features were potentially helpful in predicting the risk of a malignant outcome. The prediction could be clinically useful in the management of C3 cases.

Rationale: Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of intrahepatic cholangiocarcinoma (ICC), which is characterized by the better outcome than normal ICC. There is no report about the treatment for the metastasis of the LEL-CC. Here, we describe a rare case of LEL-CC of the liver and report the treatment for metastasis of it. Patient concerns: A 38-year-old woman with a chronic hepatitis B infection was referred to the department of liver surgery in our hospital with a mass in the liver. Diagnoses: A past ultrasound examination had revealed a 28 mm × 16 mm nodular lesion in the right posterior lobe of the liver in May 2013. She had undergone partial resection of the thyroid gland for papillary carcinoma 1 year earlier. Intervention: Suspicious of the metastasis from thyroid cancer, she underwent surgery with liver segmentectomy. The pathologic diagnosis of the lesion was LEL-CC. After surgery, she regularly got checked in our hospital, and in the 6 months after surgery, there was enlargement of lymph node before the inferior vena cava in CT. The doctor did not detect the enlargement of the lymph node until June 2017. The PET-CT was done in June of 2017, which showed the lymph node was hypermetabolic. Outcomes: The patient got her second surgery for lymph node three years after the first surgery, which was proved that the lymph node was metastasis from LEL-CC. The patient was free from recurrence 9 months after surgery. Lessons: We report the first case of surgery for metastasis from LEL-CC in the liver that was diagnosed 3 years after hepatectomy. Our findings suggest that surgery could be an effective way of treating lymph node metastasis of LEL-CC and early PET-CT can help to identify metastasis.

To predict and verify the target gene of miR-27a in pancreatic cancer by combining the result of comparative proteome analysis.The bioinformatics softwares of TargetScan,PicTar and miRanda were used to predict the possible target genes of miR-27a. Based on the results of comparative proteomics analysis, possible candidates of the target genes were selected. Expression vector of target gene 3'UTR was constructed, and then target gene was verified by dual-luciferase reporter assay system. The PANC-1 and BxPC-3 pancreatic cancer cells were treated with miR-27a mimics or negative control for 48 h. Western blot analysis was used to verify alterations of protein expression of the genes.PSMA1 was selected as the candidate target gene of miR-27a by bioinformatics prediction and comparative proteome analysis. Dual-luciferase reporter assay showed that miR-27a decreased luciferase activity in cells co-transfected with pmirGLO-PSMA1-WT, compared to the negative control, although significant difference of luciferase activity was not observed in cells co-transfected with pmirGLO-PSMA1-MUT between the two groups. The protein level of PSMA1 was down-regulated in pancreatic cancer cells transfected with miR-27a mimics in comparison with pancreatic cancer cells transfected with negative control.PSMA1 is the direct target gene of miR-27a in pancreatic cancer.

To explore the effects of ezrin silencing on pancreatic cancer cell line Panc-1.Pancreatic cancer cell line Panc-1 was transfected with ezrin silencing plasmid. The proliferation and the cell cycle status were determined by CCK-8 assay and flow cytometry analysis, respectively. Cellular membrane protrusions/microvilli formation were visualized by scanning election microscopy. Colony formation assay was used to determine the cell anchor-independent growth ability in vitro. Trans-filter migration and invasion assays were performed with 8 µm pore inserts in a 24-well BioCoat chamber with/without Matrigel.Ezrin silencing decreased cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion, but had no effects on cell proliferation in vitro and cell cycle, in pancreatic cancer cell line Panc-1.Ezrin expression affects the cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion in pancreatic cancer cell line Panc-1.

MicroRNA (miRNA), small non-coding RNA consisted of 19-24 nucleotides, are able to regulate gene expression at the post-transcriptional level. The aberrant expressions of miRNA have been found in various cancers and contribute to carcinogenesis by promoting the expression of proto-oncogenes or by inhibiting the expression of tumor suppressor genes. miRNA are related closely with the oncogenesis, progression, and prognosis of tumors. The discovery of the aberrant expression of miRNA in pancreatic ductal adenocarcinoma (PDA) and its target genes are helpful for the understanding of the pathogenesis of PDA and for the early diagnosis and prediction of this disease. In this paper, we summarize the recent research advances in miRNA expression in PDA and its target genes and discuss the potential role of miRNA in the diagnosis, and treatment of PDA.

To investigate the expression of CXCR3 and its association with clinicopathologic features in breast carcinoma.The expression level of CXCR3 in 18 samples of breast cancer and corresponding normal tissues was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis. Immunohistochemistry was carried out to examine the expression of CXCR3 in 80 breast cancers, 20 fibroadenomas and 15 normal breast tissues.(1) RT-PCR and real-time RT-PCR analysis showed a higher level of CXCR3 in breast cancer tissues than that in the corresponding normal breast tissues (P0.05). (2) Immunohistochemistry analysis showed that the positive rate of CXCR3 in breast cancer tissues was significantly higher than that in fibroadenomas and the normal breast tissues (P0.05). The expression level of CXCR3 in the lymph node-positive group was higher than that in the lymph node-negative group (P0.05). The expression of CXCR3 was positively correlated with the number of lymph nodes involved by metastasis, tumor size and pTNM tumor stage (P0.05).Chemokine receptor CXCR3 was up-regulated in breast cancer, and was associated with the progression of breast cancer. CXCR3 might be a novel molecular marker to predict lymph node metastasis and prognosis of breast cancer.