Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women.

BACKGROUND: Since human papillomavirus (HPV) DNA testing has been promoted as primary screening strategy, the triage method has also evolved from morphological testing to a molecular biomarker detection to improve screening efficiency. In this study, we investigated the performance of three HPV integration hot-spots, HMGA2, LRP1B, and TP63, as potential triage markers in HPV screening tests. MATERIALS AND METHODS: This cross-sectional study was conducted from November 2016 to December 2017 in the First Affiliated Hospital of Sun Yat-sen University. Immunocytochemistry was carried out using residual cervical cell samples from 121 HPV-positive cases (23 normal, 24 cervical intraepithelial neoplasia (CIN) 1, and 74 CIN2+). RESULTS: Of the 121 cases, 77 showed completely paired for the three biomarkers. In these 77 cases, receiver operating characteristic (ROC) analysis of HMGA2 showed the best potential for detecting CIN2+ among HPV+ cases (sensitivity 70%; specificity 91.89%; AUC 0.839). TP63 was second most effective biomarker (AUC 0.838; sensitivity 80%; specificity 81.08%). In contrast, LRP1B had the smallest AUC (0.801) among the three biomarkers but had the highest sensitivity (90%) and specificity (56.76%). To test the triage value of combining the three biomarkers, logistic regression was conducted followed by ROC comparison analysis. Promisingly, the combination of the three biomarkers gave the largest AUC of 0.951 with 92.5% sensitivity and 89.1% specificity (P < .0001 compared to liquid-based cytology test by Z-test). CONCLUSIONS: A combination of HMGA2, LRP1B, and TP63 as potential biomarkers may be useful for screening during triage of HPV-positive patients, particularly for detecting CIN2 + .

Integrative miRNA analysis identifies hsa-miR-3154, hsa-miR-7-3, and hsa-miR-600 as potential prognostic biomarker for cervical cancer.

MicroRNAs, which can interfere with the translation of target mRNAs, caught a particular interest as their functions are related to human cancers. As the most common cancer in women, cervical cancer remains one of the leading cancer-related causes of death. In this study, we performed an integrative miRNA analysis to identify prognosis related miRNAs for cervical cancer. In addition, we developed an n-miRNA expression signature (risk score) to comprehensively assess the prognosis of cervical cancer, especially for survival time. Furthermore, we performed target predictions and functional enrichment analyses for the identified miRNAs to investigate their potential role in the development of disease. Univariate Cox regression models were used to assess the association between miRNAs and prognosis of cervical cancer. Three miRNAs were identified to be significantly associated with survival time of patients. Hsa-miR-3154 and hsa-miR-7-3 were significantly associated with shortened survival time and more death cases, whereas expression level of hsa-miR-600 was significantly associated with prolonged survival time. The function enrichment analysis showed the target genes of poor prognosis related miRNAs were mainly enriched in the mTOR pathway, whereas target genes of positive prognosis related miRNAs were mainly enriched in the AMPK pathway. In summary, a 3-miRNA expression signature was identified which can predict cervical cancer patient survival. The potential functions of this 3-miRNA expression signature and individual miRNAs as prognostic targets of cervical cancer were revealed by this study. Furthermore, these findings may have important implications in the understanding of the potential therapeutic method for the cervical cancer patients.

Pathological and Therapeutic Aspects of Long noncoding RNAs in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common bone malignant tumor, which is the eighth leading form of pediatric cancer. Despite the modern chemotherapeutic development of OS, a number of patients with OS have a high risk of lung metastasis and local relapse after chemotherapy. OBJECTIVE: This review study focused on the role of long non coding RNAs (lncRNAs) in OS progression, and presented update reports on OS treatment by targeting specific lncRNAs. METHOD: We have acquired information on OS and lncRNAs from scientific databases like google scholar, pubmed and scopus, and reviewed for this study. RESULTS: The lncRNAs regulate a number of biological processes, and abnormal expression of lncRNAs could play role in many cancers and other human diseases. Interestingly, some lncRNAs can act as oncogenes, while some act as tumor suppressor genes. A number of studies revealed that targeting the specific lncRNAs by RNA interferance technology may provide a novel therapeutic strategy in the treatment of OS. CONCLUSION: LncRNAs could be a promising biomarker and might be a potential therapeutic target in OS patients.

Comparison of hepatectomy with or without hepatic inflow occlusion in patients with hepatocellular carcinoma: a single-center experience.

BACKGROUND: The negative effects of hepatic inflow occlusion (HIO) on postoperative liver function of patients with hepatocellular carcinoma (HCC) after liver resection have been reported. Nevertheless, whether or not HIO could influence the long-term outcomes remains unclear. METHODS: A total of 396 patients were included in this study and divided into without occlusion (WO) group (N.=112) and HIO group (N.=284). Aiming to minimize influence of selection bias and confounding variables, we used propensity score matching (PSM) of a 0.2 caliper to balance baseline variables. Overall survival (OS) and disease-free survival (DFS) were compared by the Kaplan-Meier method. Independent prognostic factors for OS and DFS were identified by Cox proportional hazards regression model. RESULTS: PSM were used to generate 101 pairs of patients. After PSM, OS was not significantly different between WO and HIO group (1-year: 86.1% vs. 83.2%; 3-year: 61.4% vs. 61.4%; 5-year: 45.5% vs. 39.6%; P = 0.626). Similar results of DFS were obtained between WO and HIO group (1-year: 54.5% vs. 53.5%; 3-year: 30.5% vs. 28.7%; 5-year: 14.2% vs. 14.9%; P=0.873). WO and HIO groups did not differ in 30-day, 90-day mortality and rate of postoperative complications (all P>0.05). CONCLUSIONS: Our data indicates that HIO might not negatively affect the OS and DFS of HCC patients undergoing liver resection and is likely to be a safe and viable option for intraoperative blood loss control.

Factors influencing the hospitalization costs of patients with type 2 diabetes.

This study aims to research the factors influencing the hospitalization costs of patients with type 2 diabetes, so as to provide some references for reducing their economic burden. Based on the Hospital Information System of a 3A grade hospital in China, we analyzed 2970 cases with type 2 diabetes during 2005-2012. Both the number of inpatients and the hospitalization costs had increased in the study period. Using multiple linear regression analysis, we found that patients in Urban Employee Basic Medical Insurance had higher costs than those in New Rural Cooperative Medical Scheme. We also found hospitalization costs to be higher in male patients and older patients, patients who stayed more days at hospital and who had surgeries, patients who had at least 1 complication, and patients whose admission status was emergency. After standardizing the regression coefficients, we found that the hospital stay, the forms of payment, and presence of complications were the first 3 factors influencing hospitalization costs in our study. In conclusion, the hospitalization costs of patients with type 2 diabetes could be influenced by age, gender, forms of payment, hospital stay, admission status, complications, and surgery. Medical workers in the studied region should take actions to reduce the duration of hospital stay for diabetic patients and prevent relevant complications. What is more, medical insurance needs further improvement.

Cell dormancy and tumor refractory.

Metastasis of tumor cells from primary tumor and growth at secondary sites are the major cause of mortality in cancer patients. This event may occur years and even decades after successful removal of the primary tumor and adjuvant therapy. Relapse and metastasis are universally existed in various malignancies. This phenomenon is attributed to a small amount of residual tumor cells remained in host for years, which is called as dormancy. Tumor dormancy is characterized by the balanced cell proliferation and cell death, immune evasion from host, non-angiogenic feature, insufficiency of metastatic capacity, cell cycle arrest as well as resistant to conventional chemotherapy. The molecular expressing profile suggested that dormancy is a state of quiescent cancer stem-like cells (CSCs), which are more resistant to chemotherapy and targeted therapy. Hitherto, the progression on tumor dormancy is relatively slow because there are no proper experimental models and biomarkers for identifying the dormant cells. It is no doubt that clarifying the regulatory mechanism of enter or exit of dormancy will help scientists to develop targeted strategy for eliminating dormant tumor cells, and then hinder the distant relapse and metastasis for various malignancies. This review focuses on tumor dormancy, the association of tumor dormancy with CSCs and strengthens the angiogenic switch for enter or exit of dormancy. It enlightens researchers to explore and develop more specific targeted drugs for clearance of the relapse danger.