Browsing by Author "Dai, Hongji"

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    Associations between Benign Cutaneous Nevi and Risk of Type 2 Diabetes Mellitus in Men and Women: Results from Two Prospective Cohort Studies
    (Office of the Vice Chancellor for Research, 2015-04-17) Dai, Hongji; Sun, Qi; Zhang, Xi; Manson, JoAnn E.; Hu, Frank B.; Song, Yiqing
    ABSTRACT Objective: Previous studies suggest that the number of cutaneous nevi and type 2 diabetes mellitus (T2DM) are both associated with endogenous sex hormone levels. However, no prospective studies have specifically examined the relationship between the number of benign cutaneous nevi and T2DM. Research Design and Methods: We prospectively examined the associations between the number of nevi and risk of T2DM among 23,748 men (1986-2010) from the Health Professionals Follow-up Study (HPFS) and 67,050 women (1989-2010) from the Nurses' Health Study (NHS). Information on the numbers of melanocytic nevi on arms and the incidence of T2DM was collected by validated questionnaires. Results: During 1,831,118 person-years of follow-up, we documented 8748 incident cases of T2DM. After adjustment for age, BMI, and other diabetes risk factors, the number of nevi was significantly associated with increased risk of T2DM. Multivariable-adjusted HRs (95% CIs) for <1, 1-5, 6-14, and ≥15 nevi were 1.00 (reference), 1.02 (0.92, 1.14), 1.10 (0.87, 1.38), and 1.70 (1.22, 2.36), respectively, for men (P trend = 0.03) and 1.00 (reference), 1.15 (1.09, 1.21), 1.25 (1.11, 1.40), and 1.70 (1.38, 2.09), respectively, for women (P trend = 0.019). This positive association remained consistent across subgroups of participants. Conclusions: Mole count may represent a novel marker for development of T2DM in men and women, indicating a unique nevus development-related mechanism, possibly due to altered levels or functions of endogenous steroid sex hormones, in the pathogenesis of T2DM. Further studies are warranted to clarify the relationship of nevogenesis and T2DM and underlying mechanisms.
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    Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas
    (Elsevier, 2019) Wan, Jun; Dai, Hongji; Zhang, Xiaoli; Liu, Sheng; Lin, Yuan; Somani, Ally-Khan; Xie, Jingwu; Han, Jiali; Medical and Molecular Genetics, School of Medicine
    The majority of non-melanoma skin cancer (NMSC) is cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), which are also called keratinocyte carcinomas, as both of them originate from keratinocytes. The incidence of keratinocyte carcinomas is over 5 million per year in the US, three-fold higher than the total incidence of all other types of cancer combined. While there are several reports on gene expression profiling of BCC and SCC, there are significant variations in the reported gene expression changes in different studies. One reason is that tumor-adjacent normal skin specimens were not included in many studies as matched controls. Furthermore, while numerous studies of skin stem cells in mouse models have been reported, their relevance to human skin cancer remains unknown. In this report, we analyzed gene expression profiles of paired specimens of keratinocyte carcinomas with their matched normal skin tissues as the control. Among several novel findings, we discovered a significant number of zinc finger encoding genes up-regulated in human BCC. In BCC, a novel link was found between hedgehog signaling, Wnt signaling, and the cilium. While the SCC cancer-stem-cell gene signature is shared between human and mouse SCCs, the hair follicle stem-cell signature of mice was not highly represented in human SCC. Differential gene expression (DEG) in human BCC shares gene signature with both bulge and epidermal stem cells. We have also determined that human BCCs and SCCs have distinct gene expression patterns, and some of them are not fully reflected in current mouse models.
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    Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer
    (SpringerNature, 2016-09-06) Wu, Wenting; Wagner, Erin K.; Hao, Yangyang; Rao, Xi; Dai, Hongji; Han, Jiali; Chen, Jinhui; Storniolo, Anna Maria V.; Liu, Yunlong; He, Chunyan; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    Inference of the biological roles of lncRNAs in breast cancer development remains a challenge. Here, we analyzed RNA-seq data in tumor and normal breast tissue samples from 18 breast cancer patients and 18 healthy controls and constructed a functional lncRNA-mRNA co-expression network. We revealed two distinctive co-expression patterns associated with breast cancer, reflecting different underlying regulatory mechanisms: (1) 516 pairs of lncRNA-mRNAs have differential co-expression pattern, in which the correlation between lncRNA and mRNA expression differs in tumor and normal breast tissue; (2) 291 pairs have dose-response co-expression pattern, in which the correlation is similar, but the expression level of lncRNA or mRNA differs in the two tissue types. We further validated our findings in TCGA dataset and annotated lncRNAs using TANRIC. One novel lncRNA, AC145110.1 on 8p12, was found differentially co-expressed with 127 mRNAs (including TOX4 and MAEL) in tumor and normal breast tissue and also highly correlated with breast cancer clinical outcomes. Functional enrichment and pathway analyses identified distinct biological functions for different patterns of co-expression regulations. Our data suggested that lncRNAs might be involved in breast tumorigenesis through the modulation of gene expression in multiple pathologic pathways.