The purposes of this study were to identify risk factors for cervical lymph node metastasis and to examine the association between BRAF^V600E status and clinical features in papillary thyroid microcarcinoma (PTMC).

A total of 1,587 patients with PTMC, treated in Tianjin Medical University Cancer Institute and Hospital from January 2011 to March 2013, underwent retrospective analysis. We reviewed and analyzed factors including clinical results, pathology records, ultrasound results, and BRAF^V600E status.

Multivariate logistic regression analyses demonstrated that gender (male) [odds ratio (OR) = 1.845, P = 0.000], age (< 45 years)(OR = 1.606, P = 0.000), tumor size (> 6 mm) (OR = 2.137, P = 0.000), bilateralism (OR = 2.011, P = 0.000) and extrathyroidal extension (OR = 1.555, P = 0.001) served as independent predictors of central lymph node metastasis (CLNM). Moreover, CLNM (OR = 29.354, P = 0.000) served as an independent predictor of lateral lymph node metastasis (LLNM). Among patients with a solitary primary tumor, those with tumor location in the lower third of the thyroid lobe or the isthmus were more likely to experience CLNM (P < 0.05). Univariate analyses indicated that CLNM, LLNM, extrathyroidal extension, and multifocality were not significantly associated with BRAF^V600E mutation.

The present study suggested that prophylactic neck dissection of the central compartment should be considered in patients with PTMC, particularly in men with tumor size greater than 6 mm, age less than 45 years, extrathyroidal extension, and tumor bilaterality. Among patients with PTMC, BRAF^V600E mutation is not significantly associated with prognostic factors. For a better understanding of surgical management of PTMC and the risk factors, we recommend multicenter research and long-term follow-up.

The oncoprotein, hepatitis B X-interacting protein (HBXIP), has been reported to play an important role in human malignancies. However, its functions in non-small cell lung cancer (NSCLC) are poorly understood. The goal of the present study was to identify the role of HBXIP in the regulation of NSCLC development.

The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses, and its relationships with clinicopathological features and outcomes were statistically evaluated. The effects of HBXIP on NSCLC cell progression were assessed through cell viability, colony formation, and flow cytometry analyses in vitro. The mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot, immunofluorescence, and immunoprecipitation assays. In addition, in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP knockdown.

HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of NSCLC. The high expression of HBXIP in NSCLC was significantly correlated with gender (P = 0.033), N stage (P = 0.002), and tumor-node-metastasis stage (P = 0.008). In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation, which was consistent with the enhanced cell cycle arrest in G1 phase. The results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of MEK1. In addition, the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor growth.

Taken together, our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway, which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.