Chengpei Zhu

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.

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.

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.

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.

Combined hepatocellular cholangiocarcinoma: Controversies to be addressed.

Combined hepatocellular cholangiocarcinoma (CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions.

A new avenue for obtaining insight into the functional characteristics of long noncoding RNAs associated with estrogen receptor signaling

Estrogen receptor signalling plays important regulatory roles in multiple mammalian physiological processes. Dysregulation of estrogen receptor (ER) expression and/or its associated signalling pathway is strongly associated with the development, progression, transition, and endocrine-resistance of breast cancer. Non-coding transcripts are essential regulators of almost every level of gene regulation. However, few long non-coding transcripts (lncRNAs) associated with the estrogen receptor signalling pathway have been well-described. We used array-based methods to identify 33 estrogen receptor agitation-related (ERAR) lncRNAs. A coding–non-coding gene co-expression network analysis suggested that 15 ERAR lncRNAs were associated with mitosis, DNA damage, and DNA repair. Kaplan–Meier analysis indicated that five ERAR lncRNAs selected using the Random Forest-Recursive Feature Elimination algorithm were significantly correlated with endocrine resistance-free survival and distant metastasis-free survival as well as disease free survival. Our results suggest that ERAR lncRNAs may serve as novel biomarkers for guiding breast cancer treatment and prognosis. Furthermore, our findings reveal a new avenue by which estrogen receptor signalling can be further explored.

Clinicopathological Features of Gallbladder Papillary Adenocarcinoma

AbstractAlthough patients with gallbladder papillary adenocarcinoma (GBPA) appear to have better prognoses than patients with other pathological subtypes of gallbladder carcinoma (GBC), the clinicopathological features and outcomes of GBPA have not been fully explored. This study therefore analyzed the clinicopathological characteristics and outcomes of GBPA.This study included 16 patients with GBPA and 101 with gallbladder adenocarcinoma (GBA) not otherwise specified (NOS), all diagnosed pathologically after surgical resection. Clinicopathological and survival data were retrospectively collected and compared.Fever was significantly more common in GBPA (7/16 vs 10/101; P = 0.000). Serum carbohydrate antigen 19-9 level was increased in 1 of 9 patients with GBPA and 39 of 76 with GBA (P = 0.022). More patients with GBPA underwent curative resection (15/16 vs 54/101; P = 0.009). Pathologically, patients with GBPA were at much earlier tumor (T) (4 in situ, 8 T1; P = 0.000) and Tumor, Node, Metastases (TNM) stages (P = 0.000). The overall 1-, 3-, and 5-year survival rates were significantly higher in patients with GBPA (100%, 76.9%, and 76.9%, respectively), than in patients with GBA (72.2%, 38.8%, and 31.0%, respectively; P = 0.001). Preoperative jaundice (odds ratio 7.69; 95% confidence interval, 1.53–38.76; P = 0.013) was a significant prognostic factor in patients with GBA, but was no longer significant when the patients with GBA and GBPA were pooled together.The clinicopathological features of patients with GBPA differed from those in patients with GBA (not otherwise specified). Pooling of patients may mask prognostic factors in each group.

Gallbladder papillary neoplasms share pathological features with intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct (IPNB) has been widely recognized. However, the knowledge of intracystic papillary neoplasm of the gallbladder (IPNG) including papillary adenoma and adenocarcinoma is not well defined. In this study, we compared the clinicopathological and immunohistochemical features between 32 IPNG cases and 32 IPNB cases. IPNG-1 (low-high grade dysplasia) exhibited an earlier onset age, smaller tumor size and lower level of CK20 expression compared to IPNG-2 (invasive carcinoma). Histologically, pancreaticobiliary and intestinal subtype accounted for nearly half of IPNG or IPNB (44.4% and 48.1% vs. 44.0% and 44.0%), respectively. Immunohistochemically, 88.9% of IPNG and 92.0% of IPNB cases were positive for MUC1, and 96.3% and 92.0% for CK7, respectively. CDX2 and MUC2 were more highly expressed in the intestinal subtype than in other subtypes. CK20 expression increased in parallel with tumor progression. In addition, 53.1% of IPNG cases and 68.6% of IPNB cases exhibited invasive carcinoma, and showed significant survival advantages to conventional gallbladder adenocarcinoma and cholangiocarcinoma, respectively. In conclusion, papillary adenoma and adenocarcinoma of the gallbladder can be recognized as different pathological stages of IPNG, and they share pathological features with IPNB.