Peng Zhao

Molecular Epidemiology of Clostridium difficile Infection in Hospitalized Patients in Eastern China.

ABSTRACT Few studies on risk factors for and transmission of Clostridium difficile infection (CDI) in China have been reported. A cross-sectional study was conducted for 3 years in eastern China. Consecutive stool specimens from hospitalized patients with diarrhea were cultured for C. difficile. C. difficile isolates from these patients then were analyzed for toxin genes, genotypes, and antimicrobial resistance. A severity score for the CDI in each patient was determined by a blinded review of the medical record, and these scores ranged from 1 to 6. A total of 397 out of 3,953 patients (10.0%) with diarrhea were found to have CDI. Severity of CDI was mild to moderate, and the average (± standard deviation) severity score was 2.61 ± 1.01. C. difficile was isolated from stool specimens in 432 (10.9%) of all the patients who had diarrhea. C. difficile genotypes were determined by multilocus sequence analysis and PCR ribotyping; sequence type 37 (ST37)/ribotype 017 (RT017) (n = 68, 16.5%) was the dominant genotype. Eleven patients (16.2%) with this genotype had a CDI severity score of 5. Overall, three RTs and four STs were predominant; these genotypes were associated with significantly different antimicrobial resistance patterns in comparison to all genotypes (χ2 = 79.56 to 97.76; P < 0.001). Independent risk factors associated with CDI included age greater than 55 years (odds ratio [95% confidence interval], 26.80 [18.76 to 38.29]), previous hospitalization (12.42 [8.85 to 17.43]), previous antimicrobial treatment within 8 weeks (150.56 [73.11 to 310.06]), hospital stay more than 3 days before sampling (2.34 [1.71 to 3.22]), undergoing chemotherapy (3.31 [2.22 to 4.92]), and undergoing abdominal surgery (4.82 [3.54 to 6.55]). CDI is clearly a problem in eastern China and has a prevalence of 10.0% in hospitalized patients. Among risk factors for CDI, the advanced age threshold was younger for Chinese patients than that reported for patients in developed countries.

Identifying the clonal origin of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms

Synchronous multifocal tumors often pose a diagnostic challenge for oncologists. The purpose of this study was to determine the clonal origin and metastatic relationship of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms. DNA samples were extracted from three masses harvested from a 50-year-old Han Chinese male patient who suffered from synchronous multifocal tumors in the pancreatic tail, upper biliary duct, and omentum at the time of diagnosis. The clonal origin of these samples was tested using two platforms: next-generation sequencing (NGS) of 390 key genes harboring cancer-relevant actionable mutations and whole-genome copy number variation (CNV) chip analysis. The NGS approach revealed high mutational concordance, and the gene CNV profiles were similar between lesions. Whole-genome CNVs for the three samples were further investigated using an Affymetrix chip. Using matched CNV chip data from The Cancer Genome Atlas (TCGA), we developed a computational model that generated tissue-specific CNV signatures for hepatocellular carcinoma, pancreatic carcinoma, and cholangiocarcinoma to accurately identify the origin of the tumor samples. After adding the patients CNV chip data to the model, all three samples were clustered into the pancreatic cancer branch. Both our NGS and CNV chip analyses suggested that clinically diagnosed synchronous pancreatic cancer and cholangiocarcinoma originated from the same cell population in the pancreas in our patient. This study highlights the use of genomic tools to infer the origin of synchronous multifocal tumors, which could help to improve the accuracy of cancer diagnosis.

Aberrant Expression of HOXA5 and HOXA9 in AML

BACKGROUND Aberrant expression of HOX gene expression has been observed in cancer. The purpose of this study was to investigate the alteration of HOXA5 and HOXA9 expression and their clinical significance in acute meloid leukemia (AML). MATERIALS AND METHODS The expression of HOXA5 and HOXA9 genes of bone marrow samples from 75 newly diagnosed AML patients and 22 healthy controls for comparison were examined by Real- time quantitative PCR (RQ-PCR) assay. Statistical analysis was conducted to evaluate HOXA5 and HOXA9 expression as possible biomarkers for AML. RESULTS The results showed that the complete remission rate (52.6%) of the patients who highly expressed HOXA5 and HOXA9 was significantly lower than that (88.9%) in patients who lowly express the genes (P=0.015). Spearmann correlation coefficients indicated that the expression levels for HOXA5 and HOXA9 genes were highly interrelated (r=0.657, P<0.001). Meanwhile, we detected significant correlations between HOXA9 expression and age in this limited set of patients (P=0.009). CONCLUSIONS The results suggest a prognostic impact of increased expression of HOXA5 and HOXA9 in AML patients.

The prognostic value of plasma soluble CD40 ligand levels in patients with nasopharyngeal carcinoma.

BACKGROUND Serum soluble CD40 ligand (sCD40L) concentrations are increased in patients with nasopharyngeal carcinoma (NPC). This study further evaluated the relationship between plasma sCD40L concentrations and long-term survival of NPC. METHODS Plasma sCD40L concentrations of 312 patients and 312 healthy controls were determined using an ELISA. The associations of plasma sCD40L concentrations with 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival were investigated by univariate and multivariate analyses. RESULTS Plasma sCD40L concentrations were substantially higher in patients than in healthy subjects and also correlated highly with tumor classification, lymph node classification and tumor node metastasis stage. sCD40L emerged as an independent predictor for 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival using univariate and multivariate Cox regression analysis. CONCLUSIONS High plasma sCD40L concentration is correlated with stage progression of NPC as well as associated with poor survival of NPC. It is suggested that sCD40L should have the potential to be a prognostic biomarker for NPC.

Seven LncRNA-mRNA based risk score predicts the survival of head and neck squamous cell carcinoma

Dysregulation of mRNAs and long non-coding RNAs (lncRNAs) is one of the most important features of carcinogenesis and cancer development. However, studies integrating the expression of mRNAs and lncRNAs to predict the survival of head and neck squamous cell carcinoma (HNSC) are still limited, hitherto. In current work, we identified survival related mRNAs and lncRNAs in three datasets (TCGA dataset, E-TABM-302, GSE41613). By random forest, seven gene signatures (six mRNAs and lncRNA) were further selected to develop the risk score model. The risk score was significantly associated with survival in both training and testing datasets (E-TABM-302, GSE41613, and E-MTAB-1324). Furthermore, correlation analyses showed that the risk score is independent from clinicopathological features. According to Cox multivariable hazard model and nomogram, the risk score contributes the most to survival than the other clinical information, including gender, age, histologic grade, and alcohol taking. The Gene Set Enrichment Analysis (GSEA) indicates that the risk score is associated with cancer related pathways. In summary, the lncRNA-mRNA based risk score model we developed successfully predicts the survival of 755 HNSC samples in five datasets and two platforms. It is independent from clinical information and performs better than clinical information for prognosis.

A naive Bayes algorithm for tissue origin diagnosis (TOD-Bayes) of synchronous multifocal tumors in the hepatobiliary and pancreatic system: A naive Bayes algorithm for tissue origin diagnosis

Synchronous multifocal tumors are common in the hepatobiliary and pancreatic system but because of similarities in their histological features, oncologists have difficulty in identifying their precise tissue clonal origin through routine histopathological methods. To address this problem and assist in more precise diagnosis, we developed a computational approach for tissue origin diagnosis based on naive Bayes algorithm (TOD‐Bayes) using ubiquitous RNA‐Seq data. Massive tissue‐specific RNA‐Seq data sets were first obtained from The Cancer Genome Atlas (TCGA) and ∼1,000 feature genes were used to train and validate the TOD‐Bayes algorithm. The accuracy of the model was >95% based on tenfold cross validation by the data from TCGA. A total of 18 clinical cancer samples (including six negative controls) with definitive tissue origin were subsequently used for external validation and 17 of the 18 samples were classified correctly in our study (94.4%). Furthermore, we included as cases studies seven tumor samples, taken from two individuals who suffered from synchronous multifocal tumors across tissues, where the efforts to make a definitive primary cancer diagnosis by traditional diagnostic methods had failed. Using our TOD‐Bayes analysis, the two clinical test cases were successfully diagnosed as pancreatic cancer (PC) and cholangiocarcinoma (CC), respectively, in agreement with their clinical outcomes. Based on our findings, we believe that the TOD‐Bayes algorithm is a powerful novel methodology to accurately identify the tissue origin of synchronous multifocal tumors of unknown primary cancers using RNA‐Seq data and an important step toward more precision‐based medicine in cancer diagnosis and treatment.

Clostridium difficile colonization in preoperative colorectal cancer patients

The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin

BackgroundThe majority of advanced biliary tract cancer (ABTC) patients will progress after gemcitabine and cisplatin (GP) doublet therapy, while the standard second-line regimen has not been established. We conducted this study to assess the efficacy and safety of second-line irinotecan and capecitabine (XELIRI) regimen vs. irinotecan monotherapy in ABTC patients progressed on GP.MethodsSixty-four GP refractory ABTC patients were randomised to either irinotecan 180 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1–10 of a 14-day cycle (XELIRI-arm) or single-agent irinotecan 180 mg/m2 on day 1 of a 14-day cycle (IRI-arm). Treatments were repeated until disease progression or unacceptable toxicity occurred.ResultsA total of 60 patients were included in the analysis. For XELIRI and IRI-arms, respectively, the median PFS was 3.7 vs. 2.4 months, 9-month survival rate 60.9% vs. 32.0%, median OS 10.1 vs. 7.3 months, and disease control rate 63.3% vs. 50.0%. The most common grade 3 or 4 toxicities were leucopaenia and neutropaenia.ConclusionsThis randomised, phase II study of irinotecan-containing regimens in good PS second-line ABTC patients showed a clear benefit of XELIRI regimen over irinotecan monotherapy in prolonging PFS, with acceptable toxicity.

MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer

BackgroundAberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation.MethodsExpression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC.ResultsMiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC.ConclusionMiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient.