A Specificity Protein 1 assists the progression of the papillary thyroid cell line by initiating NECTIN4.

AIMS: Papillary thyroid cancer (PTC) is one of the subtypes of thyroid cancer with increasing incidence worldwide, but the molecular mechanism is still unclear. BACKGROUND: Papillary thyroid cancer (PTC) is one of the subtypes of thyroid cancer with increasing incidence worldwide, but the molecular mechanism is still unclear. Studies have indicated that nectin cell adhesion molecule 4 (NECTIN4) was an oncogene and played an important role in the development and progression of PTC. Meanwhile, specificity protein 1 (SP1) expresses many important oncogenes and tumor suppressor genes. However, the relationship between NECTIN4 and SP1 in regulating PTC growth is unclear. OBJECTIVE: In the present study, reverse transcription PCR was utilized to detect the mRNA expression of NECTIN4 and SP1 in thyroid cancer cell lines and normal thyroid cell lines. Chromatin immunoprecipitation assays and luciferase reporter assays were used to study whether SP1 could bind to the promoter region of NECTIN4 and activate its transcription. The biological functions of SP1 correlated with NECTIN4 were also performed in TPC-1 and KTC1 cell lines. METHOD: The study revealed that the mRNA expression level of SP1 and NECTIN-4 showed a positive correlation and were upregulated in PTC cell lines. Moreover, the results of ChIP and luciferase reporter assays showed that SP1 could bind to the NECTIN4 promoter regions and activate the transcriptional level of NECTIN4. RESULT: The experiments in vitro showed that SP1 could promote cell proliferation, colony formation, migration, and invasion by regulating NECTIN4 in PTC cells. CONCLUSION: In conclusion, our study, for the first time, demonstrated that SP1 could control the transcriptional regulation of NECTIN4 and accelerate the growth of PTC, which may provide a new potential therapeutic target for PTC patients.

Radiomics-based signature of breast cancer on preoperative contrast-enhanced MRI to predict axillary metastasis.

Aim: This study aimed to predict axillary metastasis using radiology features in dynamic contrast-enhanced MRI. Methods: This study included 243 breast lesions confirmed as malignant based on axillary status. Most outcome-predictive features were selected using four machine-learning algorithms. Receiver operating characteristic analysis was used to reflect diagnostic performance. Results: Least absolute shrinkage and selection operator was used to dimensionally reduce 1137 radiomics features to three features. Three optimal radiomics features were used to model construction. The logistic regression model achieved an accuracy of 97% and 85% in the training and test groups. Clinical utility was evaluated using decision curve analysis. Conclusion: The novel combination of radiomics analysis and machine-learning algorithm could predict axillary metastasis and prevent invasive manipulation.

The Overexpression and Clinical Significance of AP1S1 in Breast Cancer.

Purpose: To explore the mechanism of AP1S1 in breast cancer. Methods and Results: In different datasets, we found that AP1S1 is more highly expressed in breast tumors, which was furthermore verified in our local cohort.Immune infiltration analysis showed that AP1S1 was related to a variety of immune cells. The higher AP1S1 expression was negatively correlated with a variety of immune infiltrating cells, suggesting that AP1S1 may affect cellular immunity.Clinical analysis showed that patients with higher AP1S1 expression had higher estrogen receptor gene expression and were more prone to distant metastasis and lymph node metastasis.The overall survival rate, disease-specific survival rate, and progression-free interval time were worse in the group with higher AP1S1 expression. AP1S1 may be a potential oncogene of breast cancer, and overexpression is related to the poor prognosis of breast cancer.Therefore, a nomogram was constructed, along with correlated gene analysis and functional analysis to further explore the carcinogenic mechanism, practical clinical issues, and value of AP1S1. Conclusion: AP1S1 is a potential oncogene of breast cancer.

Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women.

Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population's genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.

Clinical Analysis of BRAFV600E Mutation and Its Correlation With Sonographic Image Characteristics in Papillary Thyroid Carcinoma in Chinese Coastal Areas.

This study analyzed the characteristics of BRAFV600E mutation in papillary thyroid carcinoma (PTC) in Chinese coastal areas. We intended to identify noninvasive methods to determine BRAFV600E status in thyroid nodules prior to surgery. BRAFV600E mutation and the sonographic characteristics of thyroid nodules were investigated in 670 PTC patients in our hospital. We aimed to determine the relationship between BRAFV600E mutation and the clinicopathological and sonographic imaging characteristics of PTC. The mutation rate of the BRAFV600E was 78.2%. BRAFV600E mutation was significantly associated with central node (univariate analyses, P = .005; multivariate analyses, P < .001, odds ratio [OR] = 10.255) and lateral node metastases (univariate analyses, P = .001; multivariate analyses, P < .001, OR = 22). It was less frequent in PTC coexisting with Hashimoto's thyroiditis (univariate analyses, P = .016; multivariate analyses, P < .001, OR = .034). Nodules without blood flow had a significantly higher mutation rate of BRAFV600E in PTC patients (univariate analyses, P = .026). BRAFV600E mutation was significantly associated with high suspicion in the Thyroid Imaging Reporting and Data System 5 (univariate analyses, P = .004; multivariate analyses, P = .014, OR = 6.456). Our results strongly suggest that BRAFV600E mutation plays a potential role in lymph node metastasis (central node metastasis, OR = 10.225; lateral node metastasis, OR = 22). Some sonographic imaging features might be helpful in estimating the status of BRAFV600E preoperatively.

Upregulation of LAGE3 correlates with prognosis and immune infiltrates in colorectal cancer: A bioinformatic analysis.

BACKGROUND: Colorectal cancer (CRC) is the primary cause of cancer-related deaths worldwide. Identification of new CRC biomarkers is imperative to improve the prognosis and development of therapies against the disease. LAGE3 (L Antigen Family Member 3) functions as a tRNA modifier, although its potential role in CRC has not been fully elucidated. METHODS: RNA-seq matrix and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then subjected to survival, enrichment, and tumor microenvironment analyses using packages implemented in R. RESULTS: We found that LAGE3 was upregulated and significantly correlating with poor prognosis in multiple CRC cohorts. Additionally, multivariate Cox regression analysis revealed that LAGE3 was an independent prognostic factor in patients with CRC, whereas functional enrichment analysis indicated that it could regulate protein targeting, tRNA processing, and the PD-1/PD-L1 checkpoint pathway. Furthermore, CIBERSORT analysis indicated a negative relationship between LAGE3 and levels of infiltration for multiple immune cells, especially CD8 + T cells in CRC. Particularly, LAGE3 expression was inversely correlated with the expression of immune checkpoints as well as that of various immune cell types of signature genes. CONCLUSION: Collectively, our results indicate that high LAGE3 expression correlates with adverse prognosis and poor immune infiltration in CRC patients.

Lysophosphatidic Acid Receptor 5 (LPAR5) Plays a Significance Role in Papillary Thyroid Cancer via Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Thyroid cancer is the most common endocrine system malignancy. Scientists have done considerable research into the molecular mechanisms involved, but many mechanisms remain undiscovered. MATERIAL AND METHODS We performed a comprehensive analysis of the whole-transcriptome resequencing derived from thyroid tissues and paired papillary thyroid cancer (PTC) and showed that lysophosphatidic acid receptor 5 (LPAR5) is strongly overexpressed in thyroid carcinoma. Then, we used TPC-1 and KTC-1 to explore the effect of LPAR5 knockdown on colony formation, migration, proliferation, invasion, and apoptosis of PTC cell line cells. AKT activator was used for the recovery test. Finally, we designed proteomic experiments to explore the role of LPAR5 in the AKT pathway and the EMT process. RESULTS Cell function experiments showed that LPAR5 knockdown can significantly induce apoptosis of KTC-1 and TPC-1 cells. Furthermore, LPAR5 can promote PTC metastasis and tumorigenesis by activating the PI3K/AKT pathway and decreasing its cancer-promoting effect when using AKT agonist. We also found that LPAR5 can regulate the expression of EMT-related proteins, which affect invasion and migration. CONCLUSIONS In summary, downregulation of LPAR5 expression can inhibit the physiological process of PTC, and this phenomenon is related to the PI3K/AKT pathway and EMT.

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future. SIGNIFICANCE OF THE STUDY: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti-oncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins.

NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT.

Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial-mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.

CUX2 functions as an oncogene in papillary thyroid cancer.

BACKGROUND: In recent years, the incidence of thyroid cancer (TC), the most common endocrine malignancy, has been increasing. Emerging evidence indicates that the CUT/CUX/CDP family of proteins can play an important role in tumor development and progression by regulating many cancer-related functions. However, the molecular functions of CUX2 in TC remain unknown. METHODS: In this study, we used a series of loss-of-function experiments and Western blot analysis to investigate the function of CUX2 in TC and the mechanisms involved. RESULTS: Our data revealed that CUX2 expression levels were upregulated in papillary thyroid cancer (PTC). Functionally, CUX2 silencing significantly inhibited PTC cell line (KTC-1 and BCPAP) proliferation, colony formation, migration, invasion, and apoptosis. Furthermore, CUX2 induced epithelial-mesenchymal transition (EMT) and influenced the phosphorylation of AKT and mTOR in the PI3K-AKT-mTOR pathways. CONCLUSION: In summary, CUX2 may function as a tumor promoter in TC.

Upregulation of the long non-coding RNA SPRY4-IT1 predicts poor prognosis in breast cancer.

BACKGROUND: The upregulation of long non-coding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been observed in breast cancer (BC). However, there is no previous study of the relationship between SPRY4-IT1 and patient prognosis in BC. This study investigated the prognostic value of SPRY4-IT1 in BC patients. METHODS: The relative expression levels of SPRY4-IT1 were detected by RT-qPCR in 102 paired BC tissues and adjacent noncancerous tissues. The association of SPRY4-IT1 expression with clinicopathological features and prognosis was statistically analyzed. RESULTS: The findings revealed that the SPRY4-IT1 expression was significantly upregulated in clinical BC tissues compared to adjacent normal tissues (P < 0.001). Furthermore, the SPRY4-IT1 level was significantly associated with tumor size (P = 0.009), TNM stage (P = 0.0008) and lymph node metastasis (P = 0.01). Using a Kaplan-Meier analysis, it was shown that patients with high SPRY4-IT1 expression had a significantly poor overall survival (OS) rate (P = 0.0056) and a disease-free survival (DFS) rate (P = 0.0001). Moreover, multivariate Cox analysis revealed that SPRY4-IT1 expression was an independent poor prognostic factor for both OS (P = 0.024) and DFS (P = 0.025) in BC patients. CONCLUSIONS: SPRY4-IT1 expression is an independent prognostic factor for patients with BC and may serve as a potential biomarker to predict prognosis in BC patients.

Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer.

Accumulating evidence shows that microRNAs (miRNAs) have a critical role in the initiation and progression of types of human cancer, including breast cancer. Recent research indicated that miRNAs are also related with the chemotherapy on cancers. In this study, the expression of miR-221 in breast cancer (BC) patients' serum and cancer tissues was found to be significantly up-regulated. The results of in vitro MTT assay indicated that although the anti-miR-221 oligonucleotide alone did not influence the viability of BC cell lines markedly, it significantly promoted the cytotoxicity of cisplatin (DDP) to BC cells. Mechanistic studies demonstrated that the gene of BIM (Bcl-2 interacting mediator of cell death), a pro-apoptotic Bcl-2 family protein, was up-regulated by the knockdown of miR-221. We found that the synergetic effect of anti-miR-221 on increasing the sensitivity of MDA-MB-231 was BIM dependant. Furthermore, results of immunoprecipitation showed the up-regulated BIM directly combined with the Bax and Bak, leading to mitochondrial dysfunction. Our results suggest the anti-miR-221 could promote the cisplatin-inducing apoptosis by targeting the Bim-Bax/Bak axis in breast cancer.

Prognostic and metastatic value of phosphatase of regenerating liver-3 in invasive breast cancer.

PURPOSE: The aim of this study was to investigate the expression of the PRL-3 in human invasive breast cancer and to evaluate its clinical and prognostic significance. Its potential role in the invasive-metastatic properties of invasive breast cancer was also investigated. METHODS: Protein expression of PRL-3 was evaluated by immunohistochemistry for a consecutive series of 82 invasive human breast cancer tissues and 63 matched lymph node metastases, including PRL-3 mRNA expression analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) in malignant, nonmalignant breast tissue samples and lymph node metastases. We investigated the correlation of PRL-3 with clinicopathologic features, Overall and recurrence-free survival distribution curves were assessed using the Kaplan-Meier test and log-rank statistics, followed by Cox proportional hazards regression model. RESULTS: We found that 70.7% patients expressed a high level of PRL-3 protein in their tumors, and its over expression was positive correlated with lymph node metastasis (LNM) (P = 0.011). Moreover, The PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue, while increased expression of PRL-3 mRNA was significantly associated with LNM (P = 0.002). Univariate analysis showed that the positive expression of PRL-3 was a poor risk prognostic factor (OS, P = 0.045; RFS, P = 0.034). Multivariate analysis using the Cox regression model indicated that high PRL-3 expression was an independent unfavorable prognostic factor for RFS. CONCLUSIONS: These results strongly suggest that PRL-3 expression can indicate the potential role of LNM to some extent. Increasing the risk of tumor metastasis (OR = 3.889). Our results also imply that PRL-3 might be a novel molecular marker for predicting relapse of invasive breast cancer.