The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case–control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset.

Moon JH, et al. Endocrinol Metab. 2018 Jun;33(2):278-286. https://doi.org/10.3803/EnM.2018.33.2.278

Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues. A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays. Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology. PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.

Background: South Korea has the highest incidence of thyroid cancer in the world. Our study examined the trends in thyroid cancer incidence by the histologic type, cancer stage, and age group and explored possible factors that affected thyroid cancer trends.Methods: We conducted a descriptive epidemiological study using the national cancer registry data and cause of death data from 1999 to 2016 in South Korea. Age‐standardized rates were calculated using Segi's world standard population. Joinpoint regression analysis was applied to determine the changing point of thyroid cancer trends according to histologic type; Surveillance, Epidemiology, and End Results (SEER) summary stage; and age groups by sex.Results: The age‐standardized incidence of thyroid cancer in both men and women increased from 6.3 per 100,000 people in 1999 to 63.4 per 100,000 in 2012 but declined from 2012 to 2016, before the debates for over diagnosis of thyroid cancer began in 2014. The age‐standardized mortality rate of thyroid cancer, incidence of distant thyroid cancer, and incidence of regional and localized thyroid cancer started to decline since early 2000, 2010, and 2012, respectively. In addition, thyroid cancer prevalence in thyroid nodules showed decreasing trends from 1999–2000 to 2013–2014.Conclusions: The incidence of thyroid cancer began declining from 2012, before the debates for over diagnosis of thyroid cancer began in 2014. Changes in guidelines for thyroid nodule examinations may have affected this inflection point. Moreover, the debates for over diagnosis of thyroid cancer may have accelerated the decline in thyroid cancer.

Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.