Purpose: More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) –related HCC. Patients and Methods: Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results: We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively. Conclusion: We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.

Background Acute rejection (AR) of an organ transplant is a life-threatening complication. Currently, there are few diagnostic biomarkers suitable for clinical application. We aim to determine the potential of plasma microRNAs as biomarkers for AR. Methods Using rat orthotopic liver transplantation model and microarrays, we compared the difference in the spectrum and levels of microRNAs in both plasma and grafts between AR rats and control. AR-related plasma microRNAs were selected and validated using real-time quantification polymerase chain reaction. Plasma from AR rats with or without tacrolimus treatment was used for microRNA dynamic monitoring. To clarify the origin of AR-related plasma microRNAs, drug-induced liver damage rat model were performed and in situ hybridization was used to detect and localize the specific microRNA in allografts. Results We found that plasma miR-122, miR-192, and miR-146a was significantly up-regulated when AR occur (fold change>2; P<0.05) and the elevation could be repressed by immunosuppression. In liver injury rat model, up-regulated plasma miR-122 (fold change=22.126; P=0.002) and miR-192 (fold change=8.833; P<0.001) rather than miR-146a (fold change=1.181; P=0.594) were observed. Further study demonstrated that miR-146a was up-regulated by sixfold in microvesicles isolated from AR plasma, whereas miR-122 and miR-192 showed no distinct change. In situ hybridization revealed that the portal areas of the AR graft were brimming with lymphocytes, which showed highly intense staining for miR-146a. Conclusions Our study provides the global fingerprint of plasma microRNAs in AR rats and suggests that plasma miR-122 and miR-192 reflect liver injury, whereas miR-146a may associate with cellular rejection.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Although it has been known that hepatic stellate cells (HSCs) play critical roles in the development and progression of HCC, the molecular mechanism underlying crosstalk between HSCs and cancer cells still remains unclear. Here, we investigated the interactions between HSCs and cancer cells through an indirect co-culture system. The expressions of cellular and exosomal miR-148a-3p were evaluated by quantitative real-time PCR. Cell counting kit-8 was used for evaluating cell growth in vitro. Cell migration and invasion ability were evaluated by wound-healing and Transwell assays. Western blot, quantitative real-time PCR and Luciferase reporter assay were performed to determine the target gene of miR-148a-3p. A xenograft liver cancer model was established to study the function of exosomal miR-148a-3p in vivo.

Background and Aim: There is growing interest in how integrins play a role in cancer disease biology and what applications these may have in anti‐cancer therapeutic development. This study investigates integrin αvβ5 expression in non‐small cell lung carcinoma (NSCLC) and its correlations with clinical information.Methods: Tumor human tissue microarrays of 147 radically operated Chinese NSCLC patients were retrieved from the pathology archive, and sections were autoimmune stained along with positive and negative controls. Integrin αvβ5 (P1F6) mouse monoclonal antibody were validated by both Western blotting and immunoreactivity on the same set of cell pellets, according to a precedent of expression levels in cell flow cytometry. The immunoreactivity of all patients’ cases against integrin αvβ5 antibody was graded in a semi‐quantitative manner by two pathologists blind to any patient data.Results: Overall survival significantly correlated to integrin αvβ5 immunoreactivity by Cox regression analysis with P = 0.032. When applying Kaplan–Meier to analyze the comparison between positive and negative expression on lymph node metastasis patients, P = 0.082. Therefore, integrin αvβ5 expression emerges as a significant prognostic factor for NSCLC. In total, 39 of 147 (26.5%) showed an integrin αvβ5 immunoreactivity positive, as it ranged from 6.1% in squamous cell carcinoma to 19.7% in adenocarcinoma. This expression correlated significantly with histological subtypes (P = 0.007), tumor node metastasis classification of malignant tumors (P = 0.027) and lymph node metastases (P = 0.006).Conclusion: This study support the hypothesis that integrin αvβ5 is a prognostic biomarker and correlates to metastasis with therapeutic development potential in NSCLC.

The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high‐risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment. Cancer 2015;121:3157‐64. © 2015 American Cancer Society.

Background: Despite the emergence of programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs), knowledge gaps remain regarding the impact and timing of cranial radiotherapy for patients receiving anti-PD-1/PD-L1 therapy. Methods: Data were collected from 461 consecutive patients who received anti-PD-1/PD-L1 therapy for metastatic NSCLC at three institutions between June 2017 and September 2020. Intracranial progressive disease (PD) at the original disease sites, new sites, or both sites were classified as original-site PD (OPD), new-site PD (NPD), and original-and-new-site PD (ONPD), respectively. Patients with baseline BMs were categorized based on whether they received upfront cranial radiotherapy (uCRT) at any time point between the introduction of anti-PD-1/PD-L1 therapy and the first subsequent progression. Results: Of the 461 patients enrolled, 110 (23.9%) had BMs at baseline. The presence of BMs did not show independent prognostic value for progression-free survival (PFS) or overall survival (OS). During a median follow-up of 13.2 months, 96 patients with BMs developed PD, of whom 53 (55.2%) experienced intracranial PD. OPD, NPD, and ONPD were observed in 50.9%, 18.9%, and 30.2% of patients, respectively. Patients who received uCRT exhibited a longer median OS than those with BMs who did not receive uCRT (25.4 vs. 14.6 months, HR: 0.52, 95% CI: 0.29–0.91, P=0.041); this survival advantage was more prominent in patients with 1–4 BMs (median OS, 25.4 vs. 17.0 months, HR: 0.42, 95% CI: 0.22–0.81, P=0.024), and uCRT was independently associated with OS among these patients. Conclusions: The presence of BMs at baseline was not associated with poorer OS in patients with metastatic NSCLC treated with anti-PD-1/PD-L1 therapy. Intracranial progression on PD-l/PD-L1 inhibitors predominately occurred at the original BM sites. The use of uCRT may improve OS, especially in NSCLC patients with 1–4 BMs.