Identification of molecular heterogeneity of hepatocellular carcinoma based on immune gene expression signatures.

Although various molecular subtypes of hepatocellular carcinoma (HCC) have been investigated, most of these studies identify HCC subtype based on genomic profiling. Few studies have investigated the classification based on immune signatures, and none have classified HCC based on Immune activation and immunosuppressive. We performed immune gene expression of tumor tissue in 374 HCC patients from The Cancer Genome Atlas (TCGA) database and used unsupervised consensus clustering to stratify tumors. We then used HCC patients from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) as replication datasets. Based on the expression of 782 immune-related genes, HCC was stratified into four distinct immune subtypes. Tumors in one cluster (high immune activation; high-IA) indicate a higher level of Immune activation, which was characterized by higher anti-tumor immunity, higher pro-tumor immune-suppressive cell types, higher fractions of CD8+ T cells and M0 Macrophages compared with other subtypes. The high-IA also presents higher cancer-related hallmark signatures, such as epithelial-mesenchymal transition (EMT), angiogenesis, and apoptosis. We also found subpopulations of regulatory and exhaustion T lymphocyte were characterized by an opposite trend in high-IA, though samples in high-IA response to immunotherapy with better survival. The comparison of the immune profile in tumor and normal tissue indicates the activation of immune responses which only occurred in high-IA patients, while we conducted comparison of cirrhosis and non-cirrhosis tumor immune signatures, immune response activation was almost occurred in high-IA, but some of immune responses occurred in low-IA (low immune activation).

Comparable prevalence of distant metastasis and survival of different primary site for LN + pancreatic tumor.

BACKGROUND: Few studies have delved into the prevalence of distant metastasis (DM +) and survival for patients with lymph node metastases (LN +) by primary site. We aimed to detect differences in distant metastasis and prognosis between pancreatic head and bodytail tumors for LN + patients. METHODS: Patients with chemotherapy, histologically diagnosed, primary site between 2004 and 2016 were included from the SEER (Surveillance, Epidemiology, and End Results) database. Pancreatic head tumors were compared with pancreatic bodytail tumors using the odds ratio (OR) for rates of distant metastasis, hazard ratios (HR) for overall survival (OS) and cancer-specific survival (CSS). The competing risk model and propensity score matching (PSM) were performed to further explore. RESULTS: Of 5726 LN + patients identified from the SEER database, pancreatic head tumors account for 85.2% (4877 of 5726) and 14.8% (849 of 5726) were pancreatic bodytail tumors. The incidence of DM was lower in pancreatic head than in pancreatic bodytail tumors (OR, 0.29; 95% CI 0.23-0.37; P < 0.001). The multivariate Cox regression show pancreatic head tumors have a significantly shorter survival rate relative to pancreatic bodytail (HR, 1.12; 95% CI 1.03-1.22; P = 0.008), but the primary site was not a significant independent risk factor for prognosis by log-rank test (P = 0.39) and multivariate competing risk model [subdistribution HR (SHR), 1.08; 95% CI 0.98-1.19; P = 0.087].We then examined our conclusion by 1:1 propensity score matching, and the result reflected pancreatic head tumors have a lower risk of DM compared with pancreatic bodytail tumors (OR, 0.22; 95% CI 0.15-0.34; P < 0.001), but the primary site of pancreatic tumors was not associated with LN + patient survival based on univariate Cox regression (HR, 1.04; 95% CI 0.93-1.17; P = 0.435) and competing risk analysis (SHR, 1.01; 95% CI 0.89-1.12; P = 0.947). CONCLUSIONS: LN + pancreatic head tumors were significantly lower risk of DM relative to pancreatic bodytail tumors. Survival outcome in LN + pancreatic tumors didn't exist significant differences split by primary site, which indicates that the prognosis of LN + patients with chemotherapy isn't associated with the primary site of metastasis, but with the occurrence of metastasis.

FOXO3a expression and its diagnostic value in pancreatic ductal adenocarcinoma.

FOXO3a (FKHRL1) is an important regulator of cell apoptosis, proliferation, metabolic state and longevity. FOXO3a expression can be measured and has been regarded as a tumor suppressor factor in many cancers. However, the expression and role of FOXO3a in PDAC have not been defined. We evaluated the expression of FOXO3a in PDAC and the relationship of its expression with clinicopathological features and patient outcomes. We found that compared with normal tissues, the expression of FOXO3a was significantly higher in tumor tissues (P<0.001). FOXO3a expression correlates significantly with tumor differentiation and with the primary location of the tumor (P<0.001 and P=0.005, respectively). In a univariate analysis, we found that FOXO3a expression has a strong relationship with survival (P=0.013). In addition, Kaplan-Meier survival curves indicated that a low expression of FOXO3a in tumor tissues has a significantly shorter OS compared with patients with high expression of FOXO3a (P=0.013). In conclusion, the expression of FOXO3a is significantly higher in PDAC compared with normal pancreatic tissues and has a low expression or negative staining in poorly differentiated PDAC, which seems to indicate that FOXO3a expression in tumor tissues may be related to the pathological progression stage and may be used as a diagnostic indicator with early tumors.

Castleman's disease combined with choledocholithiasis: a case report and review of literature.

Castleman's disease (CD) is a rare lymphoproliferative disease with unclear pathogenesis. CD is divided into unicentric and multicentric according to clinical classification, and is usually successfully treated with surgical resection alone. CD is also classified into hyaline vascular, plasma cell, or mixed cell type according to histopathological type. CD can occur in any part of the lymphatic tissue, but most occur in mediastinal lymph node, followed by the neck, armpit, and abdominal lymph nodes. Here, we have reported a case of Castleman disease which was accidently discovered during the operation of common bile duct calculi. The histological presentation of the lymph nodes was corresponded to the plasma cell type of CD. To our knowledge, there is no report about the plasma cell type of Castleman's disease coexistence with common bile duct calculi. Finally we also review the literature.