Pan-cancer analysis from multi-omics data reveals AAMP as an unfavourable prognostic marker.

OBJECTIVES: Angio-associated migratory cell protein (AAMP) is a protein that participates in cell migration and is reported to be involved in cancer progression. However, the molecular mechanism of AAMP in pan-cancer is not known. METHODS: We used multi-omics data, such as TIMER, TCGA, GTEx, CPTAC, HPA, and cBioPortal to analyze AAMP expression, and gene alteration in pan-cancer. Univariate Cox regression and Kaplan-Meier were utilized to explore prognostic significance of AAMP expression level. We applied Spearman analysis to investigate the correlation between AAMP and TMB, MSI, immune cell infiltration, immune checkpoints. Moreover, we mainly studied liver hepatocellular carcinoma(LIHC) to explore AAMP expression, clinical significance, and prognosis. Cox regression analysis was used to study independent factor to predict prognosis for AAMP in LIHC. GSEA was utilized to investigate the biological function for AAMP in LIHC. RESULTS: AAMP was overexpressed in most cancers, and high AAMP expression was associated with worse overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) for LIHC and adrenocortical carcinoma (ACC). Moreover, AAMP had the highest mutation frequency in uterine corpus endometrial carcinoma (UCEC). AAMP was correlated with TMB and MSI in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), lung squamous cell carcinoma (LUSC), and thyroid carcinoma (THCA). Then, we focus on LIHC to investigate the expression and prognosis of AAMP. AAMP overexpression was related to histological grade and pathological stage in LIHC. Multivariate Cox regression analysis revealed that AAMP overexpression was an independent adverse prognostic marker for LIHC. AAMP expression was correlated with immune cell infiltration and immune checkpoints in LIHC. Function enrichment analysis indicated the participation of AAMP in the cell cycle and DNA replication. CONCLUSIONS: AAMP was a latent prognostic indicator for pan-cancer and had high potential as a biomarker for the diagnosis and prognosis of LIHC.

Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment.

Background: To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB). Methods: A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry. Results: In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR+CD38dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR+CD38hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR+CD38hi subset percentage. The persistent high proportion of HLA-DR+CD38hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR+CD38hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR+CD38hi subsets significantly increased, but it was still lower than that at the baseline level. Conclusions: The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR+CD38hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR+CD38hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.

SEPT9 Gene Methylation as a Noninvasive Marker for Hepatocellular Carcinoma.

BACKGROUND: Early detection appears to be the most effective approach to improve the overall survival of patients with hepatocellular carcinoma (HCC). We evaluated the potential performance of plasma SEPT9 methylation (mSEPT9) as a noninvasive biomarker for the diagnosis of patients with HCC. METHODS: A total of 373 subjects were included, and the group consisted of 104 HCC patients, 95 with an at-risk disease, and 174 healthy controls (HC). The methylation of mSEPT9 was determined using methylation-specific fluorescence quantitative PCR. The diagnostic performance of plasma mSEPT9 for HCC was assessed in a single-blind manner. RESULTS: The receiver operating characteristic (ROC) curve showed that plasma mSEPT9 can be used to detect and discriminate HCC with an area under the ROC curve (AUROC) of 0.961, a sensitivity of 82.7%, and specificity of 96.0% from HC. These results showed that plasma mSEPT9 had better diagnostic performance than serum alpha fetoprotein (AFP) (AUROC 0.881, sensitivity 57.7%, and specificity 98.3%). Similar results were noted in the detection of early-stage HCC. When combined with serum AFP, the sensitivity increased to 91.3% and 87.7% for the detection of HCC and early-stage HCC,respectively. Notably, the levels of plasma mSEPT9 dramatically decreased after surgery (P = 0.001). CONCLUSIONS: Plasma SEPT9 methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC and can be used to evaluate the therapeutic efficacy of HCC treatment.

Simultaneous radiofrequency ablation combined with laparoscopic splenectomy: a safe and effective way for patients with hepatocellular carcinoma complicated with cirrhosis and hypersplenism.

Purpose: This study aimed to evaluate the safety and effectiveness of simultaneous radiofrequency ablation (RFA) combined with laparoscopic splenectomy (Lap-Sp) for patients with hepatocellular carcinoma (HCC) complicated with cirrhosis and hypersplenism.Material and methods: Between January 2013 and June 2014, 42 patients with primary HCC complicated with cirrhosis and hypersplenism who underwent simultaneous RFA combined with Lap-Sp were enrolled at the Department of General Surgery, Beijing Di Tan Hospital. The median number of tumors ablated using RFA was one (range 1-3), and the median sum of the maximum diameter of tumors was 2.5 cm (range 1.2-5.4 cm). The related indicators before and after surgery, complications, and long-term effects were retrospectively analyzed.Results: The median operative time for 42 patients undergoing simultaneous RFA combined with Lap-Sp was 4.5 h (range 2.5-8.5 h), and the median blood loss was 120 mL (range 5-2200 mL). The incidence of moderate-to-severe postoperative complications and the perioperative mortality after surgery were 31.0 and 0%, respectively. The disease-free survival rate for one, three, and five years was 73.8, 19.7, and 16.4%, respectively. The overall survival rate was 90.5, 73.3, and 60.4%, respectively.Conclusion: Simultaneous RFA combined with Lap-Sp was safe and effective for patients with HCC complicated with cirrhosis and hypersplenism.

Short- and long-term outcomes of conversion in laparoscopic gastrectomy for gastric cancer.

PURPOSE: In laparoscopic gastrectomy (LG) for gastric cancer, conversion to open gastrectomy may sometimes be unavoidable. This study aimed to investigate the short-term and long-term outcomes of conversion from LG to open gastrectomy in patients with gastric cancer. METHODS: Patients with gastric cancer who underwent LG from January 2010 to December 2016 were included in this study. Patients were divided into a laparoscopic group and a conversion group based on the occurrence of conversion to open gastrectomy during LG. We carried out a retrospective analysis of the clinical and follow-up data of patients. Univariate and multivariate analysis were carried out on factors affecting prognosis. RESULTS: In this study, the conversion rate of patients was 8%. The most common reason for conversion to open gastrectomy was bleeding, followed by adhesions. Compared with those in the laparoscopic group, the conversion group had longer operation time, greater intraoperative blood loss, longer time to first flatus and longer hospitalization time. They also had higher incidence of postoperative complications, but the rates of major complications were similar in both groups. Patients in both groups had similar pathological results. During the follow-up period, the tumor recurrence rates in both groups were similar. There were no statistical differences in the 5-year overall survival (OS) and 5-year disease-free survival (DFS) in both groups. On multivariate analysis, tumor invasion depth and lymph node metastasis were independent predictors of OS. Tumor invasion depth, lymph node metastasis, and cancer differentiation were independent predictors of DFS. CONCLUSION: The long-term outcomes of patients with gastric cancer who were converted to open gastrectomy during LG are similar to those who did not undergo conversion.

Pancreatic carcinosarcoma with rare long-term survival: Case report and review of the literature.

PATIENT CONCERNS: We report a rare case of pancreatic carcinosarcoma involving a 44-year-old woman. The patient complained of discomfort associated with the upper abdomen and jaundice of skin and sclera for 1 week. DIAGNOSES: After hospitalization, relevant examinations were completed. The disease was diagnosed as carcinoma of the pancreatic head. INTERVENTIONS: Whipple procedure was conducted in May 2013. Intraoperative exploration indicated 2 components of the tumor: a fish-shaped gray matter and a hard structure similar to cancellous bone. Histopathological examination showed adenocarcinoma and osteosarcoma. After surgery, the patient received 8 cycles of chemotherapy with gemcitabine and raltitrexed. OUTCOMES: Previous studies indicated poor prognosis for pancreatic carcinosarcoma. However, our patient survived for 31 months with no recurrence till date. LESSONS SUBSECTIONS: Coexistence of pancreatic adenocarcinoma and osteosarcoma is very rare. Our case was also an exception in manifesting longer survival than expected.

[Non-invasive predictive model of esophageal varices in cirrhosis].

OBJECTIVE: To analyze the non-invasive indexes for predicting esophageal varices (EV) in liver cirrhosis, and to establish a model for predicting the degree of EV. METHODS: A total of 294 patients with liver cirrhosis and portal hypertension were divided into the following groups according to EV grade as assessed by endoscopy: non-EV and grade I EV, grade II EV and grade III EV. The non-invasive EV predictive measures of liver stiffness (LS), platelet (PLT) count, spleen thickness (ST), PLT/ST ratio, portal vein diameter, portal vein flow velocity and Child-Pugh score (CPS) were assessed by univariate analysis and multivariate logistic regression analysis, and used to generate a predictive model. The t-test, chi-square test, logistic analysis and receiver operating characteristic (ROC) curve were used in statistical analyses. RESULTS: The area under the ROC for the new model was 0.990. The best cutoff value for the score was 0.898, as defined from the ROC. The sensitivity of the model was 96.5%, and the specificity was 99.2%. CONCLUSIONS: The model for predicting EV was composed of LS, PLT count, ST, PLT/ST and CPS, which was accurate and sensitive, and could be used to predict EV in clinic.

Prognostic value of CYP2W1 expression in patients with human hepatocellular carcinoma.

CYP2W1 overexpression has been reported in a variety of human cancers. However, the role of CYP2W1 in hepatocellular carcinoma (HCC) remains unclear. This study was designed to evaluate the expression and prognostic significance of CYP2W1 in human HCC. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was conducted to detect CYP2W1 messenger RNA (mRNA) expression in 41 pairs of fresh-frozen HCC tissues and adjacent noncancerous tissues. In addition, CYP2W1 expression was analyzed by immunohistochemistry in 133 clinicopathologically characterized HCC cases. The relationship between CYP2W1 expression and clinicopathological features was analyzed by appropriate statistics. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between CYP2W1 expression and prognosis of HCC patients. The relative mRNA expression of CYP2W1 was significantly higher in HCC tissues than in adjacent noncancerous tissues (P < 0.001). In addition, CYP2W1 expression was significantly correlated with tumor size (P = 0.023), histological differentiation (P = 0.04), and tumor stage (P = 0.014). The Kaplan-Meier survival curves indicated that patients with high expression of CYP2W1 had shorter overall survival than those with low expression (P < 0.001). Furthermore, Cox regression analyses showed that CYP2W1 expression was an independent predictor of overall survival. Our data suggest that CYP2W1 could play an important role in HCC and might serve as a valuable prognostic marker and potential target for gene therapy in the treatment of HCC.