Anqiang Wang

Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

Intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. According to the immunohistochemical profiles of the mucin core proteins, IPNBs are classified into four types: pancreaticobiliary, intestinal, gastric, and oncocytic. Approximately 40%-80% of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma, suggesting that IPNB is a disease with high potential for malignancy. It is difficult to make an accurate preoperative diagnosis because of IPNBs low incidence and the lack of specificity in its clinical manifestation. The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation. Simultaneous proximal and distal bile duct dilation can be detected in some cases, which has diagnostic significance. Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions. However, pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion. Surgical resection is the major treatment. Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved. Staging, histologic subtype, curative resection and lymph node metastasis are factors affecting long-term survival.

Long non-coding RNA expression profiles of hepatitis C virus- related dysplasia and hepatocellular carcinoma

Recently, long non-coding RNAs (lncRNAs) were found to be implicated in cancer progression. However, the contributions of lncRNAs to Hepatitis C virus-related hepatocellular carcinoma (HCC) remain largely unknown. Here, we characterized lncRNA expression in 73 tissue samples from several different developmental stages of HCV-related hepatocarcinogenesis by repurposing microarray data sets. We found that the expression of 7 lncRNAs in preneoplastic lesions and HCC was significantly different. Among these significantly differently expressed lncRNAs, the lncRNA LINC01419 transcripts were expressed at higher levels in early stage HCC compared to dysplasia and as compared with early stage HCC, lncRNA AK021443 level increase in advanced stage HCC while lncRNA AF070632 level decrease in advanced stage HCC. Using quantitative real-time reverse-transcription PCR, we validated that LINC01419 was significantly overexpressed in HBV-related and HCV-related HCC when compared with matched non-tumor liver tissues. Moreover, functional predictions suggested that LINC01419 and AK021443 regulate cell cycle genes, whereas AF070632 is associated with cofactor binding, oxidation-reduction and carboxylic acid catabolic process. These findings provide the first large-scale survey of lncRNAs associated with the development of hepatocarcinogenesis and may offer new diagnostic biomarkers and therapeutic targets for HCV-related HCC.

Coffee and cancer risk: A meta-analysis of prospective observational studies

Meta-analyses on coffee and cancer incidence mainly restricted to limited cancers. We carried out a more comprehensive meta-analysis of cohort studies to explore association between coffee and most cancer types. We conducted comprehensive search and summarized relative risk (RR) and 95% confidence intervals for the highest versus lowest coffee intake and cancer using STATA12. We conducted dose-analysis if result suggested significant association. The publication bias was evaluated with begg’s and egger’s test. Finally, 105 individual prospective studies were included. Inverse associations were observed on oral, pharyngeal, colon, liver, prostate, endometrial cancer and melanoma, with RR 0.69 (95% CI = 0.48–0.99, I2 = 73.4%, P = 0.044), 0.87 (95% CI = 0.78–0.96, I2 = 28.4%, P = 0.007), 0.46 (95% CI = 0.37–0.57, I2 = 0%, P = 0), 0.89 (95% CI = 0.84–0.93, I2 = 30.3%, P = 0.003), 0.73 (95% CI = 0.67–0.80, I2  = 0%, P = 0) and 0.89 (95% CI = 0.80–0.99, I2  = 0%, P = 0.031) respectively. However, the relative risk for lung cancer is 2.18 (95% CI = 1.26–3.75, I2  = 63.3%, P = 0.005). The summary relative risk for increment of 2 cups of coffee were RR = 0.73, 95% CI = 0.67–0.79 for liver cancer, RR = 0.97, 95% CI = 0.96–0.98 for prostate cancer and RR = 0.88, 95% CI = 0.85–0.92 for endometrial cancer. Accordingly, coffee intake was associated with reduced risk of oral, pharynx, liver, colon, prostate, endometrial cancer and melanoma and increased lung cancer risk.

PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy

Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

Research progress and prospects of markers for liver cancer stem cells.

Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell (CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells (LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.

Citrus Fruit Intake Substantially Reduces the Risk of Esophageal Cancer: A Meta-Analysis of Epidemiologic Studies

AbstractMany epidemiologic studies indicate a potential association between fruit and vegetable intake and various cancers. The purpose of this meta-analysis is to investigate the association between citrus fruit intake and esophageal cancer risk. The authors conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Library from inception until July 2014. Studies presenting information about citrus intake and esophageal cancer were analyzed. The authors extracted the categories of citrus intake, study-specific odds ratio or relative risk, and the P value and associated 95% confidence intervals for the highest versus lowest dietary intake of citrus fruit level. The association was quantified using meta-analysis of standard errors with a random-effects model. Thirteen case–control studies and 6 cohort studies were eligible for inclusion. Citrus intake may significantly reduce risk of esophageal cancer (summary odds ratio = 0.63; 95% confidence interval = 0.52–0.75; P = 0), without notable publication bias (intercept = −0.79, P = 0.288) and with significant heterogeneity across studies (I2 = 52%). The results from epidemiologic studies suggest an inverse association between citrus fruit intake and esophageal cancer risk. The significant effect is consistent between case–control and cohort studies. Larger prospective studies with rigorous methodology should be considered to validate the association between citrus fruits and esophageal cancer.

Combination treatment including targeted therapy for advanced hepatocellular carcinoma

Management of advanced hepatocellular carcinoma (HCC), one of the most lethal cancers worldwide, has presented a therapeutic challenge over past decades. Most patients with advanced HCC and a low possibility of surgical resection have limited treatment options and no alternative but to accept local or palliative treatment. In the new era of cancer therapy, increasing numbers of molecular targeted agents (MTAs) have been applied in the treatment of advanced HCC. However, mono-targeted therapy has shown disappointing outcomes in disease control, primarily because of tumor heterogeneity and complex cell signal transduction. Because incapacitation of a single target is insufficient for cancer suppression, combination treatment for targeted therapy has been proposed and experimentally tested in several clinical trials. In this article, we review research studies aimed to enhance the efficacy of targeted therapy for HCC through combination strategies. Combination treatments involving targeted therapy for advanced HCC are compared and discussed.

Dr.VIS v2.0: an updated database of human disease-related viral integration sites in the era of high-throughput deep sequencing.

Dr.VIS is a database of human disease-related viral integration sites (VIS). The number of VIS has grown rapidly since Dr.VIS was first released in 2011, and there is growing recognition of the important role that viral integration plays in the development of malignancies. The updated database version, Dr.VIS v2.0 (http://www.bioinfo.org/drvis or bminfor.tongji.edu.cn/drvis_v2), represents 25 diseases, covers 3340 integration sites of eight oncogenic viruses in human chromosomes and provides more accurate information about VIS from high-throughput deep sequencing results obtained mainly after 2012. Data of VISes for three newly identified oncogenic viruses for 14 related diseases have been added to this 2015 update, which has a 5-fold increase of VISes compared to Dr.VIS v1.0. Dr.VIS v2.0 has 2244 precise integration sites, 867 integration regions and 551 junction sequences. A total of 2295 integration sites are located near 1730 involved genes. Of the VISes, 1153 are detected in the exons or introns of genes, with 294 located up to 5 kb and a further 112 located up to 10 kb away. As viral integration may alter chromosome stability and gene expression levels, characterizing VISes will contribute toward the discovery of novel oncogenes, tumor suppressor genes and tumor-associated pathways.

Mps1/TTK: a novel target and biomarker for cancer.

Abstract Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits. Mps1 can be utilized as a new immunogenic epitope, which is able to induce potent cytotoxic T lymphocyte activity against cancer cells while sparing normal cells. Some clinical trials have validated its safety, immunogenicity and clinical response. Thus, Mps1 may be a novel target for cancer therapy. Mps1 is differentially expressed between normal and malignant tissues, indicating its potential as a molecular biomarker for diagnosis. Meanwhile, the discovery that it clearly correlates with recurrence and survival time suggests it may serve as an independent prognostic biomarker as well.