Identification of Novel Biomarker and Therapeutic Target Candidates for Diagnosis and Treatment of Follicular Adenoma
CANCER GENOMICS & PROTEOMICS
Authors: Lai, Xianyin; Chen, Shaoxiong
Abstract
Follicular adenoma is a type of benign and encapsulated nodule in the thyroid gland, but some adenomas have the potential to progress to follicular carcinoma. Therefore, it is important to monitor the state and progress of follicular adenoma in the clinic and discover drug development targets for the treatment of follicular adenoma to prevent its worsening to follicular carcinoma. Currently, the study of biomarkers and therapeutic targets lacks applications of up-to-date technologies, including proteomics and bioinformatics. To discover novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to directly compare follicular adenoma with normal thyroid tissue samples. The proteomics analysis revealed 114 protein biomarker candidates out of 1,780 identified and quantified proteins. A comprehensive approach to prioritize the biomarker candidates by category and rank revealed CD63, DDB1, TYMP, VDAC2, and DCXR as the top five biomarker candidates. Upstream regulator analysis using the Ingenuity Pathway Analysis (IPA) software discovered four therapeutic target candidates for follicular adenoma, including TGFB1, MYC, ANGPT2, and NFE2L2. This study provided biomarker and therapeutic target candidates for a follow-up study, which will facilitate monitoring and treatment of follicular adenoma.
Pathological and diagnostic implications of DCAF16 expression in human carcinomas including adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
Authors: Liang, Chaonan; Shi, Xiuying; Fan, Chuifeng
Abstract
DCAF16 is a DDB1-CUL4 associated factor. The expression pattern of DCAF16 in human carcinomas is largely unknown. Here, we investigated DCAF16 expression in a series of human normal epithelial tissues and carcinomas using immunohistochemistry. DCAF16 expression was detected mainly in the cytoplasm in epithelial tissues including thyroid follicles (3/3), epithelium of the prostate glands (2/8), epithelium of the gastric glands (1/2), bronchial epithelium (1/1), epithelium of the intestine (1/1), and hepatocellular epithelium (3/5). There were only 2 cases showing strong immunostaining. Nuclear expression of DCAF16 was detected in a few human carcinomas (0.8%, 9/83). Cytoplasmic DCAF16 expression was detected in human carcinomas including adenocarcinoma (80.0%, 52/65), squamous cell carcinoma (30.8%, 4/13), and urothelial carcinoma (100%, 5/5). The total positive rate of DCAF16 expression was 73.5% (61/83), higher than that in normal tissues (45.8%, 11/24) (P < 0.05). The positive rate of DCAF16 expression in adenocarcinoma (80.0%, 52/65) was higher than that in squamous cell carcinoma (30.8%, 4/13) (P < 0.05). Interestingly, we found that DCAF16 expression in human carcinomas was significantly associated with a higher degree of differentiation (P < 0.05). Our results suggest that DCAF16 is expressed in various human carcinomas including adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma and is not suitable to be used as a diagnostic marker for these cancers. In addition, DCAF16 expression in human carcinomas was elevated compared with that in normal epithelial tissues, suggesting its possible role in oncogenesis. However, the mechanism involved in elevation of DCAF16 expression and its function in human carcinoma needs to be further investigated.