ObjectiveSince there are few studies exploring genes associated with lymphatic metastasis of thyroid carcinoma (THCA), this study was conducted to explore genes associated with lymphatic metastasis of THCA and to investigate the relationship with immune infiltration.MethodsDifferentially expressed genes associated with THCA lymphatic metastasis were analyzed based on The Cancer Genome Atlas Program (TCGA) database; a protein-protein interaction(PPI)network was constructed to screen for pivotal genes. Based on the identified hub genes, their expression in THCA with and without lymphatic metastasis were determined. Functional enrichment analysis was performed. The correlation between the identified genes and immune cell infiltration was explored. LASSO logistic regression analysis was performed to determine the risk score of the most relevant gene constructs and multifactor COX regression analysis based on genes in the risk score formula.ResultsA total of 115 genes were differentially expressed in THCA with and without lymphatic metastasis, including 28 upregulated genes and 87 downregulated genes. The PPI network identified seven hub genes (EVA1A, TIMP1, SERPINA1, FAM20A, FN1, TNC, MXRA8); the expression of all seven genes was upregulated in the group with lymphatic metastasis; Immuno-infiltration analysis showed that all seven genes were significantly positively correlated with macrophage M1 and NK cells and negatively correlated with T-cell CD4+ and myeloid dendritic cells. LASSO logistic regression analysis identified the five most relevant genes (EVA1A, SERPINA1, FN1, TNC, MXRA8), and multi-factor COX regression analysis showed EVA1A, SERPINA1 and FN1 as independent prognostic factors.ConclusionSeven genes were associated with lymphatic metastasis of THCA and with tumor immune cell infiltration.
Purpose: To determine the effect of miR-30a-5p on hepatoma cell radiosensitivity and elucidate the underlying mechanism.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used tomeasure miR-30a-5p expression in HepG2 and THLE-3 cells. After 4-Gy X-ray irradiation or miR-30a-5p mimic transfection, the miR-30a-5p level in HepG2 cells was determined using qRT-PCR. Luciferase reporter assay was used to confirm the correlation between miR-30a-5p and glucose-regulated protein 78 (GRP78) levels, while the effects of miR-30a-5p on the viability of HepG2 cells were determined using clone formation and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays. Apoptotic cells were evaluated by flow cytometry whereas the protein levels of GRP78, B-cell lymphoma-2 (Bcl-2), BCL2-Associated X Protein (Bax), and cleaved-caspase-9 were quantified by immunoblotting.Results: MicroRNA-30a-5p expression was decreased in HepG2 cells but reduced after 4-Gy x-ray treatment, while miR-30a-5p mimic transfection upregulated miR-30a-5p expression (p < 0.05). Cell viability was inhibited after x-ray irradiation or miR-30a-5p mimic transfection and further inhibited by irradiation + miR-30a-5p (p < 0.05). Irradiation or miR-30a-5p transfection triggered cell apoptosis; however, irradiation + miR-30a-5p induced more apoptosis, upregulated Bax and cleaved-caspase-9 expression, and reduced Bcl-2 expression (p < 0.05). MicroRNA-30a-5p also suppressed GRP78 expression.Conclusion: MicroRNA-30a-5p may enhance HCC x-ray radiosensitivity by inhibiting GRP78., and may be useful in developing treatment strategies for HCC patients.
BackgroundPapillary thyroid microcarcinoma (PTMC) is defined as a papillary carcinoma measuring ≤ 10 mm. The current management of PTMC has become more conservative; however, there are high-risk tumor features that can be revealed only postoperatively. For thyroid cancer, BRAF mutations and somatic copy number variation (CNV) are the most common genetic events. Molecular testing may contribute to clinical decision-making by molecular risk stratification, for example predicting lymph node (LN) metastasis. Here, we build a risk stratification model based on molecular profiling of thyroid fine needle aspiration (FNA) washout DNA (wDNA) for the differential diagnosis of thyroid nodules.MethodsFifty-eight patients were recruited, FNA wDNA samples were analyzed using CNV profiling through low-coverage whole genome sequencing (LC-WGS) and BRAF mutation was analyzed using quantitative PCR. FNA pathology was reported as a Bethesda System for Reporting Thyroid Cytopathology (BSRTC) score. Ultrasound examination produced a Thyroid Imaging Reporting and Data System (TIRADS) score.ResultsIn total, 37 (63.8%) patients with a TIRADS score of 4A, 13 (22.4%) patients with a TIRADS score of 4B, and 8 (13.8%) patients with a TIRADS score of 4C were recruited after ultrasound examination. All patients underwent FNA with wDNA profiling. CNVs were identified in 17 (29.3%) patients. CNVs were frequent in patients with a BSRTC score of V or VI, including eight (47.1%) patients with a score of VI and five (29.4%) with a score of V, but not in patients with a score of III, II, or I (0%). BRAF mutation was not significantly correlated with BSRTC score. LN metastasis was found more frequently in CNV-positive (CNV+) than in CNV-negative (CNV–) patients (85.7% vs. 34.6%, odds ratio = 11.33, p = 0.002). In total, three molecular subtypes of thyroid nodules were identified in this study: 1) CNV+, 2) CNV– and BRAF positive (BRAF+), and 3) CNV– and BRAF negative (BRAF–). For the CNV+ subtype, 10 (83.3%) lesions with LN metastasis were found, including four (100%) small lesions (i.e. ≤ 5 mm). For the CNV– and BRAF+ nodules, LN metastases were detected in only seven (60.0%) larger tumors (i.e. > 5 mm). For CNV– and BRAF– tumors, LN metastasis was also frequently found in larger tumors only.ConclusionsIt is feasible to identify high-risk LN metastasis thyroid cancer from FNA washout samples preoperatively using wDNA CNV profiling using LC-WGS.
Background: Breast cancer, a type of tumor associated with high heterogeneity, is top among the common malignancies threatening women's health worldwide. Emerging evidence suggests that competing endogenous RNA (ceRNA) plays a role in the molecular biological mechanisms related to the occurrence and development of cancer. However, the effect of the ceRNA network on breast cancer, especially the long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network, has not been fully studied.Methods: To explore potential prognostic markers of breast cancer under ceRNA network, we first extracted the breast cancer expression profiles of lncRNAs, miRNAs and mRNAs and their corresponding clinical data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) database. Next, we selected breast cancer-related candidate genes by intersection of the differential expression analysis and the weighted gene coexpression network analysis (WGCNA). Then, we studied the interactions among lncRNAs, miRNAs, and mRNAs by means of multiMiR and starBase and then constructed a ceRNA network of 9 lncRNAs, 26 miRNAs, and 110 mRNAs. We established a prognostic risk formula by means of multivariable Cox regression analysis.Results: Based on public databases and evaluated via modeling, we identified the HOX antisense intergenic RNA (HOTAIR)-miR-130a-3p-high mobility group-box 3 (HMGB3) axis as a potential prognostic marker in breast cancer through a prognostic risk model we established using multivariable Cox analysis. Conclusions:For the first time, the potential interactions among HOTAIR, miR-130a-3p, and HMGB3 in the tumorigenesis were clarified, and these may provide novel prognostic value for breast cancer treatment.
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