Pan-cancer analysis of NUP155 and validation of its role in breast cancer cell proliferation, migration, and apoptosis.

NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

Identification of lncRNA FAM83H-AS1 as a novel prognostic marker in luminal subtype breast cancer.

BACKGROUND: Luminal subtype breast cancer accounts for a predominant number of breast cancers. Considering the heterogeneity of the disease, it is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choices. Long non-coding RNA (lncRNA) represents an emerging and understudied class of transcripts that play a significant role in cancer biology. Growing knowledge of cancer-associated lncRNAs contributes to the development of molecular markers for prognosis evaluation and gene therapy. MATERIALS AND METHODS: Three pairs of primary luminal subtype breast cancer tissues and adjacent non-cancerous tissues were collected and sequenced. EBseq algorithm was used to identify differentially expressed lncRNAs. RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used to validate the robustness of our RNA-seq results. Kaplan-Meier and Cox regression analyses were utilized to assess the association between the lncRNAs and overall survival of patients in TCGA cohort. RESULTS: A total of 796 lncRNAs were significantly dysregulated in luminal subtype breast cancer, including 436 upregulated and 360 downregulated lncRNAs. Among them, FAM83H antisense RNA 1 (FAM83H-AS1) was the most upregulated lncRNA, whereas GSN antisense RNA 1 (GSN-AS1) was the most downregulated lncRNA. Moreover, we proved that the high expression level of FAM83H-AS1 indicated unfavorable prognosis not only in luminal subtype breast cancer but also in all subtype breast cancers. To the best of our knowledge, this is the first report indicating that FAM83H-AS1 was involved in luminal subtype breast cancer and was an independent prognostic indicator. CONCLUSION: Our study provides a rich resource to the research community for further identifying lncRNAs with diagnostic and therapeutic potentials and exploring biological function of lncRNAs in luminal subtype breast cancer.

Co-expression networks revealed potential core lncRNAs in the triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with unfavorable outcome. It is urgent to explore novel biomarkers and potential therapeutic targets in this malignancy. Increasing knowledge of long noncoding RNAs (lncRNAs) significantly deepens our understanding of cancer biology. Here, we sequenced eight paired TNBC tumor tissues and non-cancerous tissues, and validated significantly differentially expressed lncRNAs. Gene ontology (GO) and pathway analysis were used to investigate the function of differentially expressed mRNAs. Further, potential core lncRNAs in TNBC were identified by co-expression networks. Kaplan-Meier analysis also indicated that breast cancer patients with lower expression level of rhabdomyosarcoma 2 associated transcript (RMST), one of the potential core lncRNAs, had worse overall survival. To the best of our knowledge, it was the first report that RMST was involved in breast cancer. Our research provided a rich resource to the research community for further investigating lncRNAs functions and identifying lncRNAs with diagnostic and therapeutic potentials in TNBC.

Overexpression of miR-221 is associated with aggressive clinicopathologic characteristics and the BRAF mutation in papillary thyroid carcinomas.

Correlation between clinicopathogenetic features and the expression of specific miRNAs is unclear in papillary thyroid carcinoma (PTC). We therefore sought to assess whether miR-221 was associated with aggressive clinicopathologic characteristics and the BRAF mutation. We studied the expression levels of miR-221 using northern blot quantitated by scion image in 51 cases of PTCs. The status of BRAF of PTCs was analyzed through direct DNA sequencing. Mann-Whitney U test was used to analyze different expression of miR-221 in PTCs with distinct clinicopathogenetic characteristics including gender, age, tumor size, multifocality, extrathyroidal invasion, disease stages, node metastasis, and BRAF status. Compared with the normal thyroid tissues, the relative expression of miR-221 in tumor tissues was significantly upregulated (p < 0.001). Overexpression of miR-221 was significantly associated with extrathyroidal invasion (p = 0.001), lymph node metastasis (p = 0.046), advanced disease stages III-IV (p = 0.001), and the BRAF mutation (p = 0.014). While among BRAF wild tumors, miR-221 was only associated with extarthyroidal invasion, it showed strong association with all above aggressive features among BRAF mutation tumors. MiR-221 may be of potential importance in determining the aggressive properties of PTCs including the BRAF mutation, and it may further refine the risk stratification by BRAF mutation in PTCs.

Preoperative BRAF mutation is predictive of occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma.

BACKGROUND AND OBJECTIVE: The optimal resection extent for clinically unilateral papillary thyroid microcarcinoma (PTMC) remains controversial. The objective was to investigate risk factors associated with occult contralateral carcinoma, and put emphasis on the predictive value of preoperative BRAF mutation. MATERIALS AND METHODS: 100 clinically unilateral PTMC patients all newly diagnosed, previously untreated were analyzed in a prospective cohort study. We assessed the T1799A BRAF mutation status in FNAB specimens obtained from all PTMC patients before undergoing total thyroidectomy (TT) and central lymph node dissection (CLND) for PTMC. Univariate and multivariate analyses were used to reveal the incidence of contralateral occult cancer, difference of risk factors and predictive value, with respect to the following variables: preoperative BRAF mutation status, age, gender, tumor size, multifocality of primary tumor, capsular invasion, presence of Hashimoto thyroiditis and central lymph node metastasis. RESULTS: 20 of 100 patients (20%) had occult contralateral lobe carcinoma. On multi-variate analysis, preoperative BRAF mutation (p = 0.030, OR = 3.439) and multifocality of the primary tumor (p = 0.004, OR = 9.570) were independent predictive factors for occult contralateral PTMC presence. However, there were no significant differences between the presence of occult contralateral carcinomas and age, gender, tumor size, capsular invasion, Hashimoto thyroiditis and central lymph node metastasis. CONCLUSIONS: Total thyroidectomy, including the contralateral lobe, should be considered for the treatment of unilateral PTMC if preoperative BRAF mutation is positive and/or if the observed lesion presents as a multifocal tumor in the unilateral lobe.

The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma.

BACKGROUND: This study analyzed the utility of BRAF mutation screening of ultrasonography-guided fine-needle aspiration biopsy (FNAB) specimens for predicting aggressive clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC). METHODS: We assessed the T1799A BRAF mutation status in FNAB specimens obtained from 61 PTMC patients before undergoing operations for PTMC. We examined whether the BRAF mutation was associated with clinicopathologic characteristics in PTMC. Additionally, we reviewed the BRAF mutation status, and clinical, ultrasound (US), hematological, and pathology records of the patients and analyzed the associations between these characteristics and lateral lymph node metastasis (LNM). RESULTS: Analysis of the preoperative FNABs accurately reflected the BRAF status of the resected tissues in 19 of the 20 paired samples (95% concordance). We observed that the BRAF mutation was statistically significantly associated with multifocality, extrathyroidal invasion, lateral LNM, and advanced tumor stages III and IV. The BRAF mutation, pathologic features (central LNM), and US features (upper pole location) were independent predictive factors for lateral LNM in a multivariate analysis with odds ratios of 18.144 (95% confidence interval [95% CI], 1.999-164.664; P = 0.01), 8.582 (95% CI, 1.014-76.662; P = 0.049) and 9.576 (95% CI, 1.374-66.728; P = 0.023), respectively. CONCLUSIONS: BRAF mutation-positive PTMCs were more likely to manifest aggressive characteristics (extrathyroidal extension and LNM). The BRAF mutation screening of FNAB specimens can be used to predict aggressive clinicopathological characteristics of PTMC. Lateral neck nodes should be meticulously analyzed for cases of PTMC demonstrating the following three characteristics: BRAF mutation, central LNM, and US features in the upper pole location.