Association between gut microbiota and hepatocellular carcinoma and biliary tract cancer: A mendelian randomization study.

BACKGROUND: An increasing number of studies have begun to discuss the relationship between gut microbiota and diseases, yet there is currently a lack of corresponding articles describing the association between gut microbiota and hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). This study aims to explore the relationship between them using Mendelian randomization (MR) analysis method. AIM: To assess the relationship between gut microbiota and HCC and BTC. METHODS: We obtained Genome-wide association study (GWAS) data for the gut microbiome from the intestinal microbiota genomic library (MiBioGen, https://mibiogen.gcc.rug.nl/). Additionally, we accessed data pertaining to HCC and BTC from the IEU open GWAS platform (https://gwas.mrcieu.ac.uk/). Our analysis employed fundamental instrumental variable analysis methods, including inverse-variance weighted, MR and Egger. To ensure the dependability of the results, we subjected the results to tests for multiple biases and heterogeneity. RESULTS: During our investigation, we discovered 11 gut microbiota linked to an increased risk to BTC and HCC. The former included the genus Eubacterium hallii group (P = 0.017), Candidatus Soleaferrea (P = 0.034), Flavonifractor (P = 0.021), Lachnospiraceae FCS020 (P = 0.034), the order Victivallales (P = 0.018), and the class Lentisphaeria (P = 0.0.18). The latter included the genus Desulfovibrio (P = 0.042), Oscillibacter (P = 0.023), the family Coriobacteriaceae (P = 0.048), the order Coriobacteriales (P = 0.048), and the class Coriobacteriia (P = 0.048). Furthermore, in BTC, we observed 2 protective gut microbiota namely the genus Dorea (P = 0.041) and Lachnospiraceae ND3007 group (P = 0.045). All results showed no evidence of multiplicity or heterogeneity. CONCLUSION: This study explores a causal link between gut microbiota and HCC and BTC. These insights may enhance the mechanistic knowledge of microbiota-related HCC and BTC pathways, potentially informing therapeutic strategies.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes.

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

Detection of the clarithromycin resistance of Helicobacter pylori in gastric mucosa by the amplification refractory mutation system combined with quantitative real-time PCR.

The goal of this study was to evaluate the feasibility of detecting Helicobacter pylori clarithromycin resistance in gastric mucosa using the amplification refractory mutation system combined with quantitative real-time PCR (ARMS-PCR). Gastric mucosal specimens (150) were collected from patients who were unsuccessfully treated for H. pylori eradication. Each specimen was divided into 2 samples. One sample was used to extract genomic DNA and detect any gene mutations of H. pylori produced by ARMS- PCR. Sequencing was used to assess the accuracy of this method. The other sample was used to culture H. pylori. The E-test minimum inhibitory concentration (MIC) was used to assess clarithromycin resistance. The results were compared with a paired chi-square test to validate the coincidence rate among the 3 methods. The coincidence rate between the sequencing and ARMS-PCR results was 98.7%, thus verifying the accuracy of ARMS-PCR. E-tests detected 144 clarithromycin resistance cases, including 45 sensitivity cases; the resistance rate was 70%. The coincidence rate between the results of the E-test and ARMS-PCR was 97.1%, and no significant difference between the 2 methods was observed. ARMS-PCR is a simple and fast method that has high sensitivity and specificity and can be used to detect the clarithromycin resistance of H. pylori in gastric mucosa. ARMS-PCR is expected to be used to study drug resistance mechanisms and use in assays of individual therapies for H. pylori eradication.

Application of AFP whole blood one-step rapid detection kit in screening for HCC in Qidong.

Hepatocellular carcinoma (HCC) is a big problem in China where the Hepatitis B (HBV) infection patients are near to 120 million. Early screening and diagnosis is the key to reduce the incidence and mortality of HCC. Serum AFP detection is the main methods for diagnosis, recurrent monitoring and therapeutic evaluation of primary HCC. Hepatitis patients should detect the AFP at least once every six months to help early diagnosis of HCC. Unfortunately, most hepatitis and other liver disease patients do not test their AFP regularly. Therefore, a rapid, convenient detect kit for AFP is necessary for the hepatitis patients to test AFP at home by themselves. It will be very helpful to the HCC early screening and early diagnosis. We screened 859 individuals who were HBsAg positive and had high risk of HCC in Qidong by using two different kits, AFP one-step rapid detection kit (Shanghai Outdo Biotech) and AFP Diagnostics ELISA kit (Zhengzhou Autobio Diagnostics), and compared the results. As a result, the positive accordance rate and the negative accordance rate of AFP one-step rapid detection kit and the Autobio ELISA kit were 95.65% (22/23) and 99.40% (831/836), respectively. The total diagnose accordance rate reached up to 99.30% (853/859). The screening results showed a high accordance rate of two methods. It is so meaningful to achieve home-test and improve HCC early screening and diagnosis by using AFP one-step rapid detection kit.

Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo.

Metformin, an oral biguanide drug used to treat type 2 diabetes, has displayed anticancer activities in several types of cancer cells. The combination of gemcitabine and cisplatin is the standard chemotherapy regimen for cholangiocarcinoma, but its benefit is limited. The present study aimed to investigate whether metformin could enhance the activities of gemcitabine and cisplatin against cholangiocarcinoma, and the underlying mechanisms. Metformin inhibited the proliferation of human cholangiocarcinoma RBE and HCCC-9810 cells and induced cell cycle arrest at the G0/G1 phase by increasing the activation of AMP-activated protein kinase (AMPK) pathways. Metformin upregulated the expression of p21Waf1 and p27kip1, and downregulated the expression of cyclin D1, a key protein required for cell cycle progression. The combination of gemcitabine and cisplatin inhibited the proliferation and induced the apoptosis of human cholangiocarcinoma cells by inducing the phosphorylation of AMPK, downregulating cyclin D1, and activating caspase-3. Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3. Given that metformin has been used to treat type 2 diabetes patients for over half a century due to its superior safety profile, the results presented here indicate that metformin may be a potent agent for enhancing the efficacy of gemcitabine and cisplatin in the treatment of cholangiocarcinoma.

The characteristics of oesophageal squamous cell carcinoma: an analysis of 1317 cases in southeastern China.

AIM OF THE STUDY: To research the demographic and histopathological features of ESCC in southeastern China. MATERIAL AND METHODS: We retrospectively reviewed the ESCC cases in the biobank of the National Engineering Centre for Biochip in Shanghai, which cooperates with lots of hospitals and research institutions in southeastern China. The patients were pathologically confirmed as having ESCC. The demographic and histopathological features of these cases were analysed subsequently. RESULTS: A total of 1317 patients were enrolled. The overall male: female ratio was 2.88: 1. 74.34% of these cases occurred in people aged between 50-70 years. Dysphagia was the most common symptom, which accounted for 93.40% of all the patients. Stage II and III were predominant (79.73%). 72.89% of patients had a tumour length greater than 3 cm. Most of the tumours (65.83%) were located in middle third of the oesophagus. There was a significant difference among the tumour stage, length, and location in different sex groups (P < 0.05), but not between different age groups (P > 0.05). In males, ESCC is usually located in the lower parts, with a longer tumour length and higher tumour stage. 24.15% of patients had lymph nodes ratio (LNR) > 0.2. CONCLUSIONS: In our analysis, dysphagia was more common in ESCC patients, to whom more attention should be paid. Additionally, males had a higher incidence, with longer and more distant disease, which gives a poor prognosis.

In situ hybridization analysis of the expression of miR-106b in colonic cancer.

BACKGROUND: MicroRNA-106b (miR-106b) is thought to be an oncogenic microRNA that promotes tumor growth and metastasis. The potential predictive value of miR-106b was studied in colonic cancer patients. METHODS: The expression of miR-106b was examined in 180 colonic cancer cases using in situ hybridization (ISH) technique and was evaluated semi-quantitatively by examining the staining index. The Correlation of miR-106b expression and clinic-pathological features was analyzed by Spearman Rank Correlation. Wilcoxon signed rank test was used for assessing the expression difference of miRNA-106b between colonic cancerous and para-cancerous ones, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. RESULTS: MiR-106b was higher expressed in para-cancerous tissues, compared with colonic cancerous ones (P < 0.001). A positive correlation of miR-106b levels between colonic and para-cancerous tissues was also observed (CC = 0.523, P < 0.001). Furthermore, the expression of miR-106b was not significantly correlated with clinic-pathological parameters, including gender, age, histological grade, tumor size, pT stage, pN stage, pM stage and pTNM stage of the patients. Histological grade was positively correlated with pT stage (P = 0.011), pN stage (P = 0.036) and pTNM stage (P = 0.009). Patients expressing high levels of miR-106b both in colonic cancer tissues and para-cancerous ones have a relatively longer survival time but the difference is not statistically significant (P = 0.16). CONCLUSIONS: The expression difference of miR-106b levels between colonic tissues and para-cancerous tissues is statistically significant, but the miR-106b levels were not quite correlated with clinic-pathological characteristics and overall survival times of patients with colonic cancer. Lower levels of miR-106b may be connected with neoplastic effects due to interference with TGF-ß signaling, providing evidence that down-regulation of miR-106b might also play an important role in the progression of the disease. The study results are consistent with the literature and support the notion that miR-106b is an oncogenic microRNA.

Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration.

PURPOSE: Monocarboxylate transporter 4 (MCT4) is a critical component in the glycolytic metabolism of cancer cells, and is also important for malignant behavior. We investigated the expression profile of MCT4, its prognostic value in hepatocellular carcinoma (HCC) patients, its role in HCC cell proliferation and metastasis, and associated initial molecular mechanism. METHODS: MCT4 expression was examined through immunohistochemical staining of pathological specimens from 318 HCC patients who had undergone hepatectomy. The HCC cell lines were used to validate the relationship between MCT4 expression and cell proliferation, migration, and invasion. RESULTS: The results show that high MCT4 expression is indicative of elevated alpha fetoprotein levels and larger tumor size, which leads to poorer disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis shows that MCT4 expression is an independent prognostic factor for DFS and OS in HCC patients. In 91 recurrent HCC patients who underwent transarterial chemoembolization (TACE) treatment, low MCT4 expression predicted an effective treatment response and improved OS. Furthermore, in cell line experiments with MCT4 siRNA, cancer cell proliferation, migration, and invasion were closely correlated with the MCT4 expression. Knockdown of MCT4 was associated with down-regulation of phosphorylated AKT and HIF-1α. CONCLUSIONS: MCT4 expression can predict survival and TACE treatment response for HCC patients. Furthermore, MCT4 plays an important role in HCC cell proliferation, migration, and invasion. The inhibition of MCT4 can induce inactivation of HIF-1α and inhibit phosphorylation of AKT. MCT4 may be a potential therapeutic target for the treatment of HCC.

Association of the expression of unc-51-Like kinase 1 with lymph node metastasis and survival in patients with esophageal squamous cell carcinoma.

Unc-51-Like Kinase 1 (ULK1) is regarded as a central role in autophagy. Although the details of how ULK1 triggers autophagy are obscure, the relationship between ULK1 expression and the diagnosis and prognosis of cancer patients may guide the clinical practice and scientific research. The aim of this study was to investigate and compare the expression level of ULK1 in 86 paired esophageal squamous cell carcinoma (ESCC) and paracancerous tissues, and to examine the effect of ULK1 expression on the prognosis of ESCC patients. ULK1 was primarily expressed in cytoplasm, but was rarely seen in nucleus. The levels of cytoplasmic ULK1 in ESCC tissues were higher than those in paracancerous tissue (P < 0.01) and significantly associated with lymph node metastasis (LNM) (P = 0.025). Survival analysis showed that patients with low expression of cytoplasmic ULK1 had worse survival time than those with high expression of cytoplasmic ULK1 (hazard ratio = 1.754, 95% confidence interval: 1.022-3.010, P = 0.041), which disappeared after adjustment for TNM stages and LNM (P = 0.319). In conclusion, ULK1 might play an important role in the occurrence and development of ESCC and represent a potential prognostic biomarker for ESCC patients. However, the precise impact of ULK1 on predicting the prognosis of patients with ESCC requires further investigation.

Long-term survival of patients with hepatocellular carcinoma with inferior vena cava tumor thrombus treated with sorafenib combined with transarterial chemoembolization: report of two cases and literature review.

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.

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.

Evaluation of Argonaute protein as a predictive marker for human clear cell renal cell carcinoma.

UNLABELLED: Argonaute subfamily proteins are involved in human organ growth and development. Recent studies found its association with human breast cancer, however, its expression profile and its prognostic value in clear cell renal cancer (ccRCC) have not been investigated. METHODS: Expression of the Argonaute proteins were assessed by immunohistochemistry (IHC) in tissue microarrays (TMA), containing paired tumor tissue and adjacent non-cancer tissue from 176 patients who had undergone surgery in hospital for histologically proven ccRCC. Prognostic value and correlation with other clinico-pathologic factors were evaluated in two classifications. RESULTS: Data showed a significant higher expression of Argonaute 1 and Argonaute 2 present in neoplastic tissues compared with that in adjacent tissue; A significant correlation existed between the higher expression of Argonaute 1 protein with the T stage, lymph node metastasis and clinical TNM (cTNM); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated Argonaute 1 and Argonaute 2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (36.3% VS 67.1%; 37.3% VS 53.9%; respectively). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of Argonaute 2 was an independent prognostic factor in renal cancer. CONCLUSIONS: In summary, our present study clarify that the aberrant expression of Argonaute in human RCC is possibly involved with tumorigenesis and development, and the Argonaute protein could act as a potential biomarker for prognosis assessment of renal cancer. Related mechanism is worthy of further investigation.

Radiofrequency ablation does not induce the significant increase of CD4(+) CD25(+) Foxp3(+) regulatory T cells compared with surgical resection in Hepal-6 tumor model.

Surgical resection (SR) and radiofrequency ablation (RFA) are all currently recognized as important and effective treatment in solid tumors. This study aimed to investigate change in level of CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells in tumor-bearing mice after SR vs. RFA and the relationship of this level with tumor progression. Hepa1-6 tumor cells were inoculated subcutaneously into C57BL/6J mice. The population of Treg cells was measured by flow cytometry at selected post-SR or post-RFA times. Tumor growth was measured by rechallenge in the contralateral flank. The tumor volume was calculated and compared with that of a control group. The correlation between the population of Treg cells and tumor volume was analyzed. A significant increase in Treg cells was observed after SR compared with the preoperative level, while the level after RFA was relatively stable. A significant difference in tumor growth between the SR and RFA groups was observed in the initial postoperative phase but not in the later phase. A correlation was found between tumor volume and level of Treg cells. Our study revealed that RFA stabilizes the level of Treg during postoperative recovery, whereas SR activates the immunosuppressive reaction by upregulating the level of such cells, promoting tumor growth.

Study on the clinical significance of Argonaute2 expression in colonic carcinoma by tissue microarray.

BACKGROUND: To study the expression levels and clinical significance of Argonaute2 (EIF2C2) on colonic carcinomas and normal tissues. METHODS: Colon tissue samples from 90 cases of colonic carcinomas and 90 normal subjects were accumulated and made into a tissue microarray containing 360 dots. Expression of Argonaute2 (EIF2C2) was detected by immunohistochemical staining of the tissue microarray. RESULTS: There was significant difference in the expression levels of Argonaute2 (EIF2C2) between colonic carcinomas and normal tissues (P<0.01). However, the expression of Argonaute2 (EIF2C2) was not related to sex, age, position, differentiation, lymphatic metastasis and clinical stage of the tumor (P>0.05). CONCLUSION: Abnormal expression of Argonaute2 (EIF2C2) may be correlated with colon tumorigenesis.

[Ilaprazole based bismuth-containing quadruple regimen for the first-line treatment of Helicobacter pylori infection: a multicenter, randomized, controlled clinical study].

OBJECTIVE: To explore the effects of 7-day quadruple regimen as the first-line therapy strategy for Helicobacter pylori(H. pylori)infection and compare the eradication rate of ilaprazole versus esoprazole-based regimen. METHODS: A total of 440 patients with H. pylori infection, who had never received H. pylori eradication treatment, were enrolled from 10 domestic hospitals from October 2010 to July 2011. Diagnosed as chronic gastritis or duodenal ulcer according to their endoscopic examination results, they were randomized into ilaprazole and(or) esoprazole-based bismuth-containing quadruple regimen group with amoxicillin and clarithromycin (n = 110 each). After a 7-day eradication treatment, all patients with duodenal ulcer received PPI (ilaprazole and(or) esoprazole) treatment for 14 days and (13)C urea breath test was performed at least 28 days after the end of therapy. The patients with failed eradication treatment underwent endoscopy examination and biopsy. H. pylori culture and detection of antibiotic-resistant genes were also performed. RESULTS: In gastritis patients, the eradication rate (per-protocol, PP value) were 78.2% (79/101) and 82.0% (82/100) in ilaprazole and esoprazole groups (P = 0.50) while the (intention-to-treat) ITT value of eradication rate were 71.8% (79/110) and 74.5% (82/110) in ilaprazole and esoprazole groups respectively (P = 0.65). And there was no statistical difference (P > 0.05). In duodenal patients, the eradication rate (PP) were 92.1% (93/101) and 91.4% (96/105) in ilaprazole and esoprazole group (P = 0.86) while the ITT value of eradication rate were 84.5% (93/110) and 87.3% (96/110) in ilaprazole and esoprazole groups respectively (P = 0.56). And no significant difference existed between two groups in gastritis and duodenal ulcer patients (P > 0.05). In total, the eradication rate was 80.1% (161/201) (PP) and 73.2% (161/220) (ITT), 91.7% (189/206) (PP) and 85.9% (189/220) (ITT) in chronic gastritis and duodenal ulcer patients respectively. The symptomatic improvements of stomachache, burning, belching and nausea remained almost unchanged. No severe side effect was observed. The point mutations for clarithromycin resistance were detected in all 53 H. pylori strains (100%) isolated from the patients with failed eradication treatment. CONCLUSIONS: The eradication rate of PPI based bismuth-containing quadruple regimen as the first-line treatment is satisfactory in chronic gastritis and duodenal ulcer patients. No significant difference exists between the effects of ilaprazole and esoprazole-based groups. And the treatment failure may be attributed mainly to the clarithromycin resistance of H. pylori.

microRNA expression pattern and its alteration following celecoxib intervention in human colorectal cancer.

Accumulating evidence suggests that aberrant expression of microRNAs (miRNAs) is involved in several diseases, including cancer. This study aimed to investigate the miRNA expression pattern and its alteration following celecoxib intervention for human colorectal cancer (CRC). The miRNA expression profiles of CRC tissues, matched adjacent normal colorectal mucosae and HT-29 cells treated with celecoxib were determined using miRNA microarray, and further confirmed using the quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). The target genes of the aberrant miRNAs in HT-29 cells treated with celecoxib were further assessed through bioinformatic analysis. Results from this study demonstrated a significant increase in the expression of 35 miRNAs and a decrease in 30 miRNAs in the carcinoma tissues compared to the normal tissues (P<0.001). Of the 28 aberrantly expressed miRNAs, 20 were upregulated and 8 were downregulated in the HT-29 cells treated with celecoxib compared to the matched control cells (P<0.01). Furthermore, miR-552 was found to be correlated with clinical stage, lymph node and distant metastases (P<0.05). Stage and distant metastases revealed differential expression of miR-139-3p and grade disclosed aberrant expression of miR-142-3p. In addition, multiple target genes involved in several essential survival pathways were found be modulated by the aberrantly expressed miRNAs in HT-29 cells treated with celecoxib. Our data revealed that a common pattern of miRNA expression in the colorectum could distinguish malignant tissue from normal mucosa. Celecoxib inhibited HT-29 cell growth in vitro which was partly attributable to the altered expression of miRNAs. miRNAs may be involved in CRC tumorigenesis and can serve as potential therapeutic targets.

Tissue microarrays in Chinese human rectal cancer: study of expressions of the tumor-associated genes.

BACKGROUNDS/AIMS: The cellular basis for rectal cancer development is still unclear. The aim of this study was to evaluate the relationship between the expression of p53, cyclinD1, bcl-2, ß-catenin, c-myc, cyclooxygenase-2 (COX-2) and nm23-H1 and the clinicopathological characteristics of rectal cancer. METHODOLOGY: Expressions of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 proteins were detected by immunohistochemical staining to two tissue microarrays containing tissues accumulated from 54 human rectal cancers and 40 para-cancer mucosa. RESULTS: Significant differences were demonstrated between the rectal cancers and their benign para-cancer counterparts according to the expressions of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 (p<0.05). Additionally, positive correlations of ß-catenin with cyclinD1 and c-myc (r=0.412, p=0.002; r=0.447, p=0.000) and of p53 with bcl-2 (r=0.332, p=0.001) were found. Cancer tissues with overexpression of ß-catenin or bcl-2 were less likely to differentiate to advanced grade. Expression of cyclinD1 had a correlation with clinical stages (p=0.039). In addition, a negative correlation was found between nm23-H1 expression and the histological grades, distance metastasis and Duke's stages. CONCLUSIONS: Aberrant expression of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 might attribute to the carcinogenesis of human rectal cancer. Furthermore, cyclinD1 and nm23-H1 might be involved in rectal cancer progression. This study recommends the application of tissue microarrays in rectal cancer research for its reliable quick throughput.

Association between polymorphism rs6983267 and gastric cancer risk in Chinese population.

AIM: To explore the association between single nucleotide polymorphisms (SNPs) at 8q24 and gastric cancer risk. METHODS: A case-control investigation including 212 gastric cancer patients and 377 healthy controls was conducted. The genotypes of SNPs (rs6983267, rs7008482 and rs10808555) were examined and established through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to evaluate the association between SNPs and gastric cancer. RESULTS: The genotype frequencies of rs6983267 in gastric cancer patients were obviously different from those in the control (P = 0.005). GT genotype of rs6983267 was associated with an increased risk of gastric cancer compared with GG genotype (adjusted odds ratio = 2.01, 95% confidence interval: 1.28-3.14). Further stratified analysis indicated that rs6983267 GT genotype facilitated the risk of gastric cancer of non-cardiac and intestinal type (OR: 2.638, 95% CI: 1.464-4.753; OR: 1.916, 95% CI: 1.166-3.150, respectively). CONCLUSION: This study demonstrates for the first time that rs6983267 is involved in susceptibility to gastric cancer, although further large-sample investigations are still needed.