Fine mapping of the MHC region identifies major independent variants associated with Han Chinese primary biliary cholangitis.

The genetic association of primary biliary cholangitis with major histocompatibility complex (MHC) has been widely confirmed among different ethnicities. To map specific MHC region variants associated with PBC in a Han Chinese cohort, we imputed HLA antigens and amino acids (AA) in 1126 PBC cases and 1770 healthy control subjects using a Han-MHC reference database. We demonstrate that HLA-DRB1 and/or HLA-DQB1 contributed the strongest signals, and that HLA-DPB1 was a separate independent locus. Regression analyses with classical HLA alleles indicate that HLA-DQB1*03:01 or HLA-DQß1-Pro55, HLA-DPB1*17:01 or HLA-DPß1-Asp84 and HLA-DRB1*08:03 could largely explain MHC association with PBC. Forward stepwise regression analyses with HLA amino acid variants localize the major signals to HLA-DRß1-Ala74, HLA-DQß1-Pro55 and HLA-DPß1-Asp84. Electrostatic potential calculations implicated AA variations at HLA-DQß1 position 55 and HLA-DPß1 position 84 as critical to peptide binding properties. Furthermore, although several critical Han Chinese AA variants differed from those shown in European populations, the predicted effects on antigen binding are likely to be very similar or identical and underlie the major component of MHC association with PBC.

Genome-wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis.

Anti-nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome-wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 × 10-22 ; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 (P = 5.78 × 10-28 ; OR, 3.89; 95% CI, 3.05-4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti-sp100-positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA-DRß1-Asn77/Arg74, DRß1-Ser37, and DPß1-Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10-9 ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.

Identification of serum miR-30a-5p as a diagnostic and prognostic biomarker in colorectal cancer.

BACKGROUND: Circulating microRNAs (miRNAs) have become increasingly appreciated in the diagnosis and prognosis of colorectal cancer (CRC). OBJECTIVE: The aim of this study was to assess the potential diagnostic and prognostic significance of serum miR-30a-5p as a potential biomarker. METHODS: The expression levels of serum miR-30a-5p were measured in 138 cases with CRC, 50 cases with benign lesions (colorectal adenoma and polyps) and 60 healthy volunteers by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: The results showed that serum miR-30a-5p levels were frequently downregulated in patients with CRC and benign lesions in comparison with normal controls. Moreover, serum miR-30a-5p levels in early-stage CRC patients were significantly increased after surgery. Receiver-operating characteristic (ROC) curve analysis demonstrated serum miR-30a-5p could well distinguish CRC patients, early-stage CRC patients from healthy controls with a relative high value of area under the curve (AUC). Furthermore, low serum miR-30a-5p expression was more frequently occurred in CRC patients with aggressive clinical variables. Additionally, CRC patients exhibiting high serum miR-30a-5p expression had significantly prolonged overall survival than those exhibiting low expression. Finally, both univariate and multivariate analyses revealed that serum miR-30a-5p expression was an independent prognostic factor for overall survival in CRC patients. CONCLUSIONS: Collectively, these findings suggested serum miR-30a-5p might act as a novel biomarker for the diagnosis and prognosis of CRC.

MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in China. Dysregulation of microRNAs (miRNAs) is involved in cancer development and progression. Our previous study showed an inverse relationship between miR-193a-3p expression and the prognosis of CRC. However, the exact biological functions of miR-193a-3p in CRC are still poorly understood. This study aimed to explore the role and mechanism of miR-193a-3p in CRC. METHODS: Real-time PCR and Western blotting were used to examine the expression levels of RNA and protein, respectively. A dual luciferase assay was performed to validate predicted targets of miR-193a-3p. Loss and gain-of-function studies were carried out to reveal the effects and potential mechanism of the miR-193a-3p in the proliferation, metastasis and angiogenesis of CRC cells. RESULTS: The expression levels of miR-193a-3p in human CRC cell lines were significantly decreased compared with that in normal colonic epithelium cell line. Furthermore, plasminogen activator urokinase (PLAU) was validated as a direct target gene of miR-193a-3p. Over-expression of miR-193a-3p inhibited proliferation, migration and angiogenesis of HT-29 cell, whereas forced expression of PLAU could rescue the inhibitory effects. CONCLUSION: miR-193a-3p might inhibit CRC cell growth, migration and angiogenesis partly through targeting PLAU. MiR-193a-3p/PLAU axis might provide a potent therapeutic opportunity for aggressive CRC.

Heterorhabditidoides chongmingensis gen. nov., sp. nov. (Rhabditida: Rhabditidae), a novel member of the entomopathogenic nematodes.

During a recent soil sample survey in Eastern China, a new entomopathogenic nematode species, collected from the Chongming Islands in the southern-eastern area of Shanghai, was discovered. Morphological characteristics of different developmental stages of the nematode combined with molecular data showed that this nematode is a new genus of Rhabditidae, and described as Heterorhabditidoides chongmingensis gen. nov., sp. nov., for that it shares more morphological characteristics with heterorhabditids than with steinernematids. For males, the papillae formula of bursa is 1, 2, 3, 3, with constant papillae number in the terminal group, stoma tubular-shaped and about 1.5 head width; cheilorhabdions cuticularized, esophageal collar present and long, median bulb present. For infective juveniles, EP=90 (80-105)microm, ES=104 (92-120)microm, tail length=111 (89-159)microm, and a=19.1 (15-21). The percentages of the nucleotides A, T, C and G in the ITS1 regions of the new species are significantly different from those of heterorhabditids and other rhabditids. Molecular phylogenetic trees based on 18S rDNA and the internal transcribed spacer (ITS) sequences data revealed that the new entomopathogenic nematode species forms a monophyletic group, which is a sister group of the clade comprised of some genera of Rhabditidae.

Molecular Phylogeny of Geographical Isolates of Bursaphelenchus xylophilus: Implications on the Origin and Spread of this Species in China and Worldwide.

The genetic diversity and phylogeny of 26 isolates of Bursaphelenchus xylophilus from China, Japan, Portugal and North America were investigated based on the D2/3 domain of 28S rDNA, nuclear ribosomal Internal Transcribed Spacer (ITS) sequences, and random amplified polymorphic DNA (RAPD) analysis. The genetic diversity analysis showed that the D2/3 domain of 28S rDNA of isolates of B. xylophilus from China, Portugal, Japan and the US were identical and differed at one to three nucleotides compared to those from Canada. ITS sequences of isolates from China and Portugal were the same; they differed at one or two nucleotides compared to those of Japanese isolates and at four and 23 nucleotides compared to those from the US and Canada, respectively. The phylogenetic analysis indicated that Chinese isolates share a common ancestor with one of the two Japanese clades and that the Canadian isolates form a sister group of the clade comprised of isolates from China, Portugal, Japan, and the US. The relationship between Japanese isolates and those from China was closer than with the American isolates. The Canadian isolates were the basal group of B. xylophilus. This suggests that B. xylophilus originated in North America and that the B. xylophilus that occurs in China could have been first introduced from Japan. Further analysis based on RAPD analysis revealed that the relationship among isolates from Guangdong, Zhejiang, Shandong, Anhui provinces and Nanjing was the closest, which suggests that pine wilt disease in these Chinese locales was probably dispersed from Nanjing, where this disease first occurred in China.

Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray.

AIM: To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis. METHODS: We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffin-embedded blocks, including carcinomas (n = 85), adenomatous polyps (n = 18), as well as normal para-cancerous colon tissues (n = 9). Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Akt1, beta-catenin, c-myc, nm23-h1 and Cox-2. RESULTS: The protein expressions of p53, bcl-2, bax, cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa (P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively). Chi-square analysis showed that the statistically significant variables were p53, p21, bax, beta-catenin, c-myc, PTEN, p-Akt1, Cox-2 and nm23-h1 for histological grade (P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively), beta-catenin, c-myc and p-Akt1 for lymph node metastasis (P = 0.011, P = 0.005, and P = 0.032, respectively), beta-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis (P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively), and cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 for clinical stages (P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively). CONCLUSION: Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, beta-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in progression of human colon cancer.

Prognostic significance of preoperative platelet-lymphocyte ratio in a Chinese cohort patient with colorectal cancer.

Cancer-related systemic inflammation affects many aspects of malignancy. The platelet-to-lymphocyte ratio (PLR), an easily applicable inflammatory marker based on platelet and lymphocyte counts, is associated with the clinical outcome of some cancers. The present study aimed to investigate the prognostic significance of the preoperative PLR in a cohort of colorectal cancer (CRC) patients. A total of 138 patients with CRC were enrolled in this retrospective study. The optimal cutoff value for the PLR was calculated using receiver operating curve (ROC) analysis. The correlation of PLR with the clinicopathological characteristics of patients was explored. Cox proportional hazard analysis was applied to determine the independent prognostic effect of PLR. PLR of 248 yielded the most optimal predictive value for the prognosis of CRC [area under the curve (AUC) = 0.820]. High level of PLR was significantly associated with lymph node and distance metastasis (P<0.001 and = 0.003, respectively), vascular and perinural invasion (P<0.001), advanced TNM stage (P<0.001), and poor differentiation (P = 0.037). Furthermore, the univariable analysis showed a significant impact of increased PLR on OS (HR = 4.326, 95% CI: 2.903-6.445, P<0.001), while this association remained significant in multivariable analysis (adjusted HR = 4.605, 95% CI: 2.786-7.611, P<0.001). Our findings indicated that elevated preoperative PLR might have potential value in predicting poor outcome in patients with CRC.

Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is an early and key process in the metastatic cascade during the progression of colorectal cancer (CRC). The aim of the present study was to identify deregulated EMT-related microRNAs (miRNAs/miRs) of CRC and assess the effect of differentially expressed miRNAs on the prognosis of patients with CRC. Genome-wide expression profiling of miRNAs was assessed in 3 EMT-negative and 3 EMT-positive CRC tissues. Differentially expressed miRNA was further validated in 90 pairs of CRC and corresponding paracarcinoma tissues using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 6 miRNAs (miR-10a-5p miR-204-3p, miR-1224-3p, miR-193a-3p, miR-365a-3p and miR-3678-3p) were identified to be differentially expressed between different EMT statuses of CRC tissues. Following validation using RT-qPCR, 3 miRNAs (miR-10a-5p, miR-365a-3p and miR-193a-3p) were selected for subsequent studies. The expression levels of miR-10a-5p, miR-193a-3p and miR-365a-3p were markedly increased compared with levels in corresponding paracarcinoma tissues. Survival analyses revealed that down-regulation of miR-193a-3p was associated with worse prognosis of patients with CRC, particularly in female and older patients. The results of the present study indicate that miR-193a-3p may be an EMT-related biomarker and serve as a novel prognostic factor for CRC.

A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13.1 (RPL3/SYNGR1). We also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC.

Gastric heterotopic pancreas masquerading as a stromal tumor: A case report.

Heterotopic pancreas (HP), a rare condition that is generally asymptomatic, is an aberration in the developmental profile of the pancreas. While it can occur in any location in the gastrointestinal tract, it is most typically found in the antrum of the stomach and is usually wrongly considered to be a submucosal tumor (SMT). Despite advances in diagnostic modalities, a HP still poses a diagnostic dilemma to clinicians. Invasive surgery or endoscopic resection have often been inappropriately applied in cases of an ectopic pancreas due to the difficulty in distinguishing it from neoplastic SMTs, such as gastrointestinal stromal tumors (GISTs). The present study reports the unusual case of a middle-aged female with an SMT at the lesser curve of the mid-body of the stomach, which was initially diagnosed as a GIST through endoscopic ultrasonography and computed tomography. However, following removal by endoscopic submucosal dissection, this lesion was finally histopathologically confirmed as an HP. Therefore, although it is rare, the possibility of an HP should always be considered when diagnosing an extramucosal gastric mass. The precise pre-operative diagnosis of this entity may avoid unnecessary extensive treatment intervention.

Prognostic significance of Glasgow prognostic score in patients with stage II colorectal cancer.

Glasgow prognostic score (GPS), one information based prognostic score, has been previously shown to be a prognostic factor in varieties cancers mostly in advanced tumors. This study aimed to explore its value in patients with relatively early stage colorectal cancer (CRC). A total of 99 CRC patients with stage II from 2005 to 2010 operated in our hospital were enrolled in this study. C-reactive protein (CRP), albumin (ALB), Karnofsky Performance Status (KPS) score as well as a variety of biochemical variables before the operation was acquired from the database retrospectively. The value of GPS was calculated and its association with the clinical factors was further investigated. The prognostic significance was analyzed by univariate and multivariate analyses. Increased preoperative GPS was found associated with elevated carcinoembryonic antigen (CEA) and decreasing of KPS. Kaplan-Meier analysis and log-rank test revealed that a higher GPS predicted a higher risk of postoperative mortality in stage II CRC (P < 0.001). Furthermore, multivariate analysis demonstrated the GPS to be a risk factor for postoperative mortality (HR 3.215; P=0.025). The preoperative GPS might be a potential useful indicator for postoperative survival in patients with stage II CRC.

Evaluation of tumor metastasis-associated markers for molecular classification in patients with esophageal squamous cell carcinoma.

This study aims to ascertain the relationship of tumor metastasis-associated markers cyclin D1, connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) with the clinicopathologic features and prognosis of patients with esophageal squamous cell carcinoma (ESCC), and to investigate their value in ESCC molecular classification. The expression of cyclin D1, CTGF and VEGF in 100 specimens from patients and 20 from normal esophageal mucosa were detected by immunohistochemistry. The relationship of their expression with prognosis of the patients with ESCC was evaluated by Cox regression model and Kaplan-Meier survival curve analysis. High levels of expression of cyclin D1, CTGF, and VEGF were observed in 61 (61%), 53 (53%), 49 (49%) cases, respectively. Univariate survival analysis indicated that the levels of expression of cyclin D1, CTGF and VEGF were associated with survival (all P-value < 0.05). Multivariate analysis indicated that cyclin D1 and VEGF were independent prognostic factors affecting the three-year survival rate of patients (P = 0.001, 0.017, respectively). Furthermore, high level expression of cyclin D1, CTGF and VEGF in stage I patients was found associated with poor three-year survival rate (all P-value < 0.05). The prognosis probably was favorable for patients with low expression of cyclin D1 even in stage III, or VEGF even in stage IV. Tumor metastasis-associated markers such as cyclin D1 and VEGF may be independent prognostic factors affecting survival rate of postoperative ESCC patients. It is possible to judge prognosis better and tailor treatments to each individual patient when these markers were applied to ESCC molecular classification.

Elevated serum level of carbohydrate antigen 19-9 in benign biliary stricture diseases can reduce its value as a tumor marker.

Although carbohydrate antigen (CA19-9) level is frequently upregulated in pancreatobiliary cancer, it is also elevated in some benign diseases. This study aimed to determine whether CA19-9 levels could be used to distinguish between benign obstructive jaundice and pancreatobiliary cancer. Fifty-seven patients with obstructive jaundice were studied retrospectively. Endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, stone extraction, or stent placement were used to treat patients with benign bile duct stricture or inoperable malignant biliopancreatic diseases, whilst surgery was performed in suitable cases. Serum CA19-9 levels and some additional biochemical parameters were evaluated before and after treatment. CA19-9 levels were elevated in most patients, along with levels of total bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT), and 10 patients with benign disorders had extraordinarily high levels of these markers (> 1000 U/mL). The mean CA19-9 level in the malignant group was greater than that in the benign group (826.83 ± 557.34 vs. 401.92 ± 483.92 U/mL, P = 0.005), and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CA19-9 were 100%, 7.69%, 33.33% and 47.47%, respectively. CA19-9 levels in the whole cohort were correlated with ALP (r = 0.77, P < 0.001), GGT (r = 0.83, P < 0.001), bilirubin (r = 0.69, P < 0.001), and CRP (r = 0.37, P = 0.004). The reduction in serum level of CA19-9 after treatment in the malignant group was remarkably less than that observed in the benign group (97.26 ± 123.24 U/mL vs. 352.71 ± 397.29 U/mL, P < 0.001). CA19-9 levels may not be sufficient to distinguish between malignant and benign obstructive jaundice diseases.

Aberrant expression of microRNAs in serum may identify individuals with pancreatic cancer.

Pancreatic cancer (PC) has the poorest survival rate among all types of human cancer due to the lack of sensitive and non-invasive diagnostic screen methods for PC screening. Our aim was to identify novel serum microRNA (miRNA) biomarkers for the early detection of PC. We used microarray to screen differential expression of miRNAs in two pooled serum samples (6 PC patients and 6 healthy controls). A panel of miRNAs (22 over-expression and 23 decreased) were deregulated in serum of PC patients in comparison to controls. The expressions of 8 selected miRNAs were further evaluated in sera from 49 PC patients and 27 controls using quantitative reverse transcription-polymerase chain reaction. The levels of serum miR-492 and miR-663a were significantly decreased in PC patients compared with controls (P < 0.05). ROC curve analysis showed that serum miR-492 and miR-663a yield an AUC of 0.787 with 75.5% sensitivity and 70.0% specificity and 0.870 with 85.7% sensitivity and 80.0% specificity, respectively, for discriminating between PC patients and healthy controls. In addition, the level of miR-663a was significantly and inversely associated with TNM stage (P = 0.027). These results suggested that serum miR-492 and miR-663a could have strong potential as novel non-invasive biomarkers for the early detection of PC.

Elevated pre-treatment levels of high sensitivity C-reactive protein as a potential prognosticator in patients with colorectal cancer.

Elevated levels of C-reactive protein (CRP) have been described as a prognostic factor in various types of human malignancy. In the present study, the prognostic potency of CRP was validated for patients with colorectal cancer (CRC) in order to guide patient management and define high-risk populations for follow-up or for therapeutic purposes. The association between the high sensitivity-CRP (hs-CRP) levels of a total of 123 patients with CRC and their clinicopathological characteristics was explored. Subsequently, univariate and multivariate analyses were performed to investigate the survival impact of pre-treatment hs-CRP levels in this cohort study. Statistically significant correlations between the serum levels of hs-CRP and lymph node and distant metastasis (P<0.001 and P=0.012, respectively), vascular and perineural invasion (P<0.001 and P<0.001), grades (P=0.022) and clinical stages (P=0.001), but not age and gender (P=0.616 and 0.676, respectively), were found. The five-year survival rate of patients with elevated (>5.0 mg/l) hs-CRP levels was demonstrated to be significantly less than that of those in the normal group (≥5.0 mg/l) by applying the Kaplan-Meier method (13.3 versus 57.0%, log-rank test P<0.001). Furthermore, following identification as a prognostic factor through using univariate analysis, high levels of hs-CRP (P<0.001) were validated as an independent prognosticator in CRC in the present study through using multivariate analysis. Pre-treatment serum CRP levels were associated with advanced and progressed CRC patients, therefore these levels may serve as a potential prognostic marker for CRC patients.

Gastrointestinal bleeding as an initial manifestation in asymptomatic multiple myeloma: A case report and review of the literature.

Multiple myeloma (MM) is an uncommon type of malignant hematological neoplasm which, besides primarily involving the bone marrow, has a potent tendency to involve other organs and to present with various clinical manifestations. Involvement of the gastrointestinal (GI) system, particularly presenting with GI hemorrhage, in the course of MM is extremely rare. In the present study, we report a case of a middle-aged male who initially demonstrated GI bleeding and was finally diagnosed with MM. Further laboratory examinations, including analysis of globulin in the blood, bone marrow aspiration and radiogram, supported this diagnosis. This case may promote the possible involvement of plasma cell myeloma in the differential diagnosis of patients with unexplained and refractory GI bleeding. In this study we also present a thorough review of the literature with regard to the association between MM and GI hemorrhage.

HER2 gene amplification in esophageal squamous cell carcinoma is less than in gastroesophageal junction and gastric adenocarcinoma.

The aim of the present study was to detect the amplification of the human epidermal growth factor receptor 2 (HER2) gene in esophageal squamous cell carcinoma (ESCC), gastroesophageal junction adenocarcinoma (GEJAC) and gastric cancer (GC), as well as to understand the pathological meaning of HER2 gene amplification with regard to clinico-pathological parameters in these types of cancer. HER2 gene amplification was evaluated by fluorescence in situ hybridization (FISH) in surgically obtained specimens from 76 cases of ESCC, 50 of GEJAC and 48 of GC, as well as 21 specimens of tumor-adjacent normal epithelium as a control group. The HER2 gene amplification rates in ESCC, GEJAC and GC were 3.9 (3/76), 24.0 (12/50) and 18.8% (9/48), respectively. The rates of HER2 gene amplification in GEJAC and GC were significantly higher compared with ESCC (χ2=11.563, P<0.001 and χ2=7.375, P<0.007, respectively). HER2 gene amplification was not detected in the normal esophageal or gastric mucosa samples. In ESCC, HER2 gene amplification was correlated with the invasion of the ESCC cells, vascular invasion and lymph node metastasis (χ2=4.789, 3.858 and 5.354, respectively; all P<0.05). However, in GEJAC and GC, no correlations were observed between HER2 amplification and the gender, age, degree of differentiation, invasion, vascular invasion and lymph node metastases of the patients (all P>0.05). The rate of HER-2 gene amplification was low in ESCC, although the amplification of HER-2 was correlated with tumor metastasis in these patients. The rates of HER-2 gene amplification in GEJAC and GC were higher compared with ESCC. Therefore, compared with ESCC, GEJAC may be more similar to GC with regard to HER-2 gene amplification features.

Cyclin A overexpression is associated with chemosensitivity to paclitaxel-based chemotherapy in patients with esophageal squamous cell carcinoma.

The aim of this study was to investigate the correlation between cyclin A expression and efficacy of paclitaxel-based chemotherapy in patients with esophageal squamous cell carcinoma (ESCC). The expression of cyclin A was examined in 48 newly diagnosed ESCC patients prior to treatment using the MaxVision immunohistochemistry method. The patients received four cycles of paclitaxel-based chemotherapy, the short-term treatment efficacy was evaluated and a 3-year follow-up was conducted. The response rate was greater in patients with positive cyclin A expression compared with those with negative expression (54.8 vs. 23.5%; χ(2)=4.373; P<0.05). Univariate and multivariate Cox analysis revealed that clinicopathological stage, degree of differentiation and expression of cyclin A were independent prognosis factors in patients with ESCC following paclitaxel-based chemotherapy. ESCC patients with positive cyclin A expression demonstrated an increased sensitivity to paclitaxel-based chemotherapy, suggesting that cyclin A may be used as a marker to predict the treatment efficacy of paclitaxel in patients with ESCC.

MicroRNA expression profiles in human colorectal cancers with liver metastases.

At present, a full understanding of the mechanisms by which colorectal cancer (CRC) distant metastases form is still beyond our reach because of the intricate regulation of gene expression. MicroRNAs (miRNAs) are shown to be involved in various human diseases including cancers through negative regulation of target gene expression at the post-transcriptional level. However, there are only a few studies on the roles of miRNA aberrations in liver metastasis of human colorectal cancer. To identify miRNA expression patterns associated with liver metastasis in human colorectal cancer, the miRNA expression profiles of colorectal cancer tissues with liver metastasis and their non-metastatic counterparts were studied using microRNA microarrays and further confirmed by quantitative RT-PCR. We show that 28 miRNAs are differentially expressed in the colorectal carcinomas with liver metastasis compared to the non-metastatic counterparts. Of these, 4 miRNAs including miR-150*, miR-125b-2*, miR-1179 and miR-139-3p were up-regulated in colorectal cancers with liver metastasis while the others were down-regulated. The target genes of selected deregulated miRNAs were predicted through bioinformatic techniques with two functional analyses, gene ontology and KEGG analysis, which showed that categories of high enrichment GOs and specific pathways targeted by dysregulated miRNAs were involved in liver metastasis during human colorectum carcinogenesis. Our results indicated that miRNAs are not only involved in carcinogenesis of colorectum, but may also participate in the progression such as with liver metastases in human colorectal cancers.