Huiqiong Yang’s research while affiliated with Tongji Medical University and other places

Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/KrasG12D+/- mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/KrasG12D+/- mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment.

Epithelial keratinocyte proliferation is an essential element of wound repair, and chronic wound conditions, such as diabetic foot, are characterized by aberrant re-epithelialization. In this study, we examined the functional role of retinoic acid inducible-gene I (RIG-I), a key regulator of epidermal keratinocyte proliferation, in promoting TIMP-1 expression. We found that RIG-I is overexpressed in keratinocytes of skin injury and underexpressed in skin wound sites of diabetic foot and streptozotocin-induced diabetic mice. Moreover, mice lacking RIG-I developed an aggravated phenotype when subjected to skin injury. Mechanistically, RIG-I promoted keratinocyte proliferation and wound repair by inducing TIMP-1 via the NF-κB signaling pathway. Indeed, recombinant TIMP-1 directly accelerated HaCaT cell proliferation in vitro and promoted wound healing in Ddx58-/- and diabetic mice in vivo. In summary, we demonstrated that RIG-I is a crucial factor that mediates epidermal keratinocyte proliferation and may be a potential biomarker for skin injury severity, thus making it an attractive locally therapeutic target for the treatment of chronic wounds such as diabetic foot.

Background The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of ROSE during the EUBS-TBNA procedure in the diagnosis of pulmonary lesions (PLs).Methods Enrolled in this study were 260 patients with nodules, masses, cavities, or inflammatory lesions on pulmonary CT images. They were assigned to undergo EBUS-TBNA with ROSE (n = 134) or without ROSE (n = 126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we further explored whether the ROSE method during EBUS-TBNA would improve the diagnostic yield and reduce the incidence of complications.ResultsThe overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE and the non-ROSE group were 29.9 and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of the ROSE method during EBUS-TBNA were 97.4, 96.9, 92.5, and 98.90%, respectively. The result of the chi-square test effectively proved that ROSE operation during EBUS-TBNA contributes to the diagnosis of malignancy compared with the non-ROSE group (χ2 = 13.858, P < 0.001). The number of punctures in the ROSE group was significantly lower than that in the non-ROSE group (P < 0.001).ConclusionROSE examination during EBUS-TBNA could effectively improve the diagnostic yield of malignant diseases compared with the non-ROSE group and reduce the number of intraoperative punctures, which is a clinical application worth popularizing.

Background: The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of EUBS-TBNA combined with ROSE in the diagnosis of peripheral pulmonary lesions (PPLs). Methods: Enrolled in this study were 260 patients with nodules, masses, cavities or inflammatory lesions on pulmonary CT images, and age ranged from 23 to 83 years old. They were assigned to undergo EBUS-TBNA with ROSE (n=134) or without ROSE (n=126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to see whether the ROSE method during EBUS-TBNA would increase the risk of procedure-related complications, improve the diagnostic yield, and evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: The number of punctures in ROSE group was significantly lower than that in non-ROSE group (P<0.001). There was no significant difference in hemoptysis between the two groups (P=0.402). The overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE-group and the non-ROSE group was 29.9% and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of ROSE during EBUS-TBNA were 97.4%, 96.9%, 92.5% and 98.90% respectively, showing a high agreement with the pathological results. Youden index reached 94.3%. Conclusions: ROSE examination during EBUS-TBNA could effectively improve the diagnostic yield and reduce the number of intraoperative punctures with the diagnostic results in cytology well consistent with those of traditional pathology, and therefore is worth promoting and applying in clinical practice.

AbaR-type genomic islands (AbaRs) are important elements responsible for antimicrobial resistance in Acinetobacter baumannii . This study performed a large-scale identification of AbaRs to understand their distribution and compositions of antimicrobial resistance genes. We identified 2.89-kb left-end and 1.87-kb right-end conserved sequences (CSs) and developed a bioinformatics approach to identify AbaRs using the CSs as signatures in 3148 publicly available genomes. AbaRs were prevalent in A. baumannii , as being found in 2091 genomes. They were sparse in other Acinetobacter species and confined only to this genus. Results from 111 complete genomes showed that over 85% AbaRs resided on chromosomes. The external flanks adjacent to the inverted repeats available in all identified CSs were mapped to an AbaR-free chromosome or search in the NCBI database for empty loci to define insertion sites. Surprisingly, 84 insertion sites were revealed with diverse origins, including 51 scattered on the chromosome, 20 plasmid-borne, 12 locating on prophages, transposons, IS Aba1 , complex AbaRs and genomic islands of other type, and one uncharacterised, and some were strongly associated with clonal lineages. Finally, we found 994 antimicrobial resistance genes covering 28 unique ones from 70.9% (299/422) intact AbaRs currently available. The resistance gene profiles displayed an apparent clonal lineage-specific pattern, highlighting the distinct features of AbaRs in global clones (GCs) 1 and 2. The tet(B ) was highly specific to the AbaRs in GC2. In conclusion, AbaRs have diverse insertion sites on the chromosome and mobile genetic elements and display distinct antimicrobial resistance gene profiles in different clonal lineages.

Many clustered protocadherin genes (PCDHs) within chromosome 5q31 are frequently down-regulated in colorectal cancer (CRC) due to the hypermethylation of this region, and some of them have been identified as tumor suppressors. However, the association between the expression of the clustered PCDHs and prognosis of CRC patients is still unclear. Here, we identified multiple PCDHs that were significantly down-regulated in CRC by analyzing the RNA-seq data of the Cancer Genome Atlas (TCGA) cohort. Among them, one γ-PCDH subfamily member, PCDHGA7, was found to be associated with overall survival in the patients with wild-type KRAS. Next, we experimentally validated the decrease of PCDHGA7 mRNA and protein levels in tumor tissues of 20 CRC patients by using quantitative real-time PCR (qRT-PCR) and Immunohistochemistry assay (IHC). To further investigate whether the expression of PCDHGA7 could predict clinical outcomes, an independent cohort of 138 patients, whose tumors carried wild-type KRAS, was enrolled. In-house tissue microarrays (TMAs) were developed to facilitate the protein detection. And prognostic significance was analyzed. The result showed low PCDHGA7 expression was associated with advanced TNM stage, high risk of tumor recurrence and short overall survival. In conclusion, this study demonstrates that PCDHGA7 is down-regulated in CRC and its expression level is correlated with clinical outcomes in patients with wild-type KRAS. Our finding indicates PCDHGA7 could serve as a potential novel biomarker to predict prognosis by combining certain tumor genotypes in patients of CRC.

MicroRNA-32 (miR-32) is associated with tumor progression and poor prognosis in certain malignant tumors. However, the function and clinical relevance of miR-32 in human hepatocellular carcinoma (HCC) has not yet been elucidated. The present study aimed to investigate the expression and prognostic value of miR-32 from liver samples in patients with HCC. The expression of miR-32 was analyzed in HCC and healthy tissues using Gene Expression Omnibus datasets. Reverse transcription-quantitative polymerase chain reaction was used to analyze the levels of miR-32 mRNA in 154 HCC liver samples, 33 of which were paired with adjacent non-tumor tissues. The overall survival (OS) rate in patients with HCC was evaluated using Kaplan-Meier survival analysis, and the factors that may affect the prognosis and survival of patients with HCC were analyzed using univariate (log-rank test) and multivariate Cox proportional hazard models. The present results demonstrated that miR-32 expression levels were significantly upregulated in HCC liver biopsies compared with normal tissues (P<0.05). miR-32 expression was significantly associated with the number of foci and tumor diameter (P<0.05). In addition, Kaplan-Meier analysis revealed that patients with low miR-32 expression had longer OS and disease-free survival compared with those with high miR-32 expression (P<0.01). Altogether, to the best our knowledge, the present study is the first study to indicate the association between increased miR-32 expression with HCC progression and poor prognosis in patients. This suggests that miR-32 may have potential prognostic value and may be used as a tumor biomarker for the diagnosis of patients with HCC.

Altered expression of microRNAs (miRNAs or miRs) contributes to lung carcinogenesis. The present study performed an in silico analysis of differentially expressed miRNAs in different peripheral blood samples from patients with various diseases vs. controls using the Gene Expression Omnibus (GEO) database data, and assessed miR-105-1 expression in 32 normal lung and 142 non-small cell lung cancer (NSCLC) tissue samples using reverse transcription-quantitative polymerase chain reaction. Survival data were calculated using Kaplan-Meier curves and a log-rank test. The stepwise forward Cox regression model was performed for univariate and multivariate analyses of independent predictor of overall survival (OS) of patients. The data on in silico and tissue microarray analyses of miRNA expression revealed reduced miR-105-1 expression in different types of human cancer, particularly in NSCLC. The level of miR-105-1 expression was confirmed to be downregulated in NSCLC tissues compared with that in normal lung tissues. Reduced miR-105-1 expression was associated with larger tumor size as well as poor OS and disease-free survival (DFS) of patients. Multivariate survival analysis demonstrated that reduced miR-105-1 expression and tumor size were independent predictors for OS of NSCLC patients. In conclusion, reduced miR-105-1 expression in NSCLC tissues is associated with poor OS and DFS of NSCLC patients.

MicroRNAs (miRNAs) serve an important role in tumorigenesis and development. Although a low expression of miR-125a in hepatocellular carcinoma (HCC) has been reported, the clinical significance remains unknown. In the current study, the data of Gene Expression Omnibus datasets was analyzed and significantly low expression of miR-125a in HCC was verified. Furthermore, the expression and clinical significance of miR-125a was investigated in 27 normal liver and 98 HCC tissue samples using reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that the level of miR-125a expression was lower in HCC biopsies compared with that in normal liver tissues. Survival analysis established that miR-125a expression was negatively associated with the prognosis of HCC. Multivariate survival analysis demonstrated that patients with HCC with lowmiR-125a and Ki67-positive expression have shorter overall, and disease-free survival times. Altogether, the results of the current study provide the first evidence that reducedmiR-125a expression is associated with HCC progression and poor prognosis in patients, suggesting that miR-125a may have potential prognostic value as a tumor biomarker for patients with HCC.

The present study was carried out to investigate the clinical significance of TMPRSS3 and TNFRSF11B in breast cancer. Thus, the expression levels of TMPRSS3 and TNFRSF11B and the correlation with prognosis in patients with breast cancer were analyzed in silico using gene microarray and hierarchical clustering analysis. Then, the differential expression in breast cancer vs. normal breast tissue was explored in the Oncomine platform and verified in our independent samples using IHC technique. Our results indicated that TMPRSS3 was upregulated and TNFRSF11B was downregulated in breast cancer tissues compared with the levels in the human normal breast tissues. TMPRSS3 and TNFRSF11B were confirmed to be correlated with distant organ metastasis of breast cancer. Moreover, upregulation of TMPRSS3 accompanied by downregulation of TNFRSF11B was found to be associated with a shorter median overall survival and indicated a poor prognosis. In conclusion, TMPRSS3 and TNFRSF11B may have potential prognostic value to be used as tumor biomarkers in breast cancer patients.