Insights into the performance of PREDICT tool in a large Mainland Chinese breast cancer cohort: a comparative analysis of versions 3.0 and 2.2.

BACKGROUND: PREDICT is a web-based tool for forecasting breast cancer outcomes. PREDICT version 3.0 was recently released. This study aimed to validate this tool for a large population in mainland China and compare v3.0 with v2.2. METHODS: Women who underwent surgery for nonmetastatic primary invasive breast cancer between 2010 and 2020 from the First Affiliated Hospital of Wenzhou Medical University were selected. Predicted and observed 5-year overall survival (OS) for both v3.0 and v2.2 were compared. Discrimination was compared using receiver-operator curves and DeLong test. Calibration was evaluated using calibration plots and chi-squared test. A difference greater than 5% was deemed clinically relevant. RESULTS: A total of 5424 patients were included, with median follow-up time of 58 months (IQR 38-89 months). Compared to v2.2, v3.0 did not show improved discriminatory accuracy for 5-year OS (AUC: 0.756 vs 0.771), same as ER-positive and ER-negative patients. However, calibration was significantly improved in v3.0, with predicted 5-year OS deviated from observed by -2.0% for the entire cohort, -2.9% for ER-positive and -0.0% for ER-negative patients, compared to -7.3%, -4.7% and -13.7% in v2.2. In v3.0, 5-year OS was underestimated by 9.0% for patients older than 75 years, and 5.8% for patients with micrometastases. Patients with distant metastases postdiagnosis was overestimated by 10.6%. CONCLUSIONS: PREDICT v3.0 reliably predicts 5-year OS for the majority of Chinese patients with breast cancer. PREDICT v3.0 significantly improved the predictive accuracy for ER-negative groups. Furthermore, caution is advised when interpreting 5-year OS for patients aged over 70, those with micrometastases or metastases postdiagnosis.

A web-based novel model for predicting prognostic value in patients with invasive micropapillary carcinoma in breast cancer: a real-world data retrospective cohort study.

Invasive micropapillary carcinoma (IMPC) accounts for less than 2% of all invasive breast cancers and usually associates with poor survival, so we investigated the prognostic factors for IMPC using a large population-based database and designed a web-based novel model. Clinicopathological prognostic factors were evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was performed to evaluate the prognostic value of variables on the overall survival. A web-based nomogram was finally constructed to predict the survival probability. The model was validated in an external dataset. A web-based model, combined with age, radiation, clinical stage, and hormone receptor (HR) immunochemistry status four prognostic factors, was constructed. The C-index (0.714, 95% CI 0.683-0.741), calibration curves, and decision curves showed that this model was superior in prediction. By determining the cut-off values, high-risk group and low-risk group were divided. The Kaplan-Meier survival curves showed that these two groups had significantly different survival rates (P < 0.0001). The result of C-index, calibration curves, and Kaplan-Meier survival curves were consistent in the validation cohort. The novel nomogram with four risk factors resulted in accurate prognostic prediction for IMPC.

L Antigen Family Member 3 Serves as a Prognostic Biomarker for the Clinical Outcome and Immune Infiltration in Skin Cutaneous Melanoma.

L Antigen Family Member 3 (LAGE3) is an important RNA modification-related protein. Whereas few studies have interrogated the LAGE3 protein, there is limited data on its role in tumors. Here, we analyzed and profiled the LAGE3 protein in skin cutaneous melanoma (CM) using TCGA, GTEx, or GEO databases. Our data showed an upregulation of LAGE3 in melanoma cell lines compared to normal skin cell lines. Besides, the Kaplan-Meier curves and Cox proportional hazard model revealed that LAGE3 was an independent survival indicator for CM, especially in metastatic CM. Moreover, LAGE3 was negatively associated with multiple immune cell infiltration levels in CM, especially CD8+ T cells in metastatic CM. Taken together, our study suggests that LAGE3 could be a potential prognostic biomarker and might be a potential target for the development of novel CM treatment strategies.

Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma.

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene. Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid. Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell. Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

Serum deprivation response functions as a tumor suppressor gene in papillary thyroid cancer.

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.

H/ACA box small nucleolar RNA 7B acts as an oncogene and a potential prognostic biomarker in breast cancer.

BACKGROUND: Breast cancer (BC) is the most frequent malignancy occurring in women worldwide. Emerging evidence indicates that small nucleolar RNAs (snoRNAs) play a role in tumor development. In the current study, we evaluated expression profiles and functions of snoRNAs associated with BC. METHODS: We analyzed the expression levels of snoRNAs between breast cancer and normal tissues in TCGA database and found that SNORA7B is upregulated in BC. We confirmed this result in clinical cancer tissues and BC cell lines via qRT-PCR. Then, we investigated clinical significance in public datasets and biological function of SNORA7B using a series of in vitro gain- and loss-of-function experiments. RESULTS: SNORA7B expression was significantly upregulated in samples from patients with BC in both public database and our clinical tissues compared to its expression in normal tissues. Meanwhile, patients with high SNORA7B expression have worse prognosis. Inhibition of SNORA7B expression impaired cell growth, proliferation, migration, and invasion via inducing apoptosis. CONCLUSIONS: SNORA7B functions as an important oncogenic snoRNA in BC and may serve as a potential prognosis biomarker for BC.

METTL7B promotes migration and invasion in thyroid cancer through epithelial-mesenchymal transition.

Thyroid cancer is associated with one of the most malignant endocrine tumors. However, molecular mechanisms underlying thyroid tumorigenesis and progression remain unclear. In order to investigate these mechanisms, we performed whole-transcriptome sequencing, which indicated that a differentially expressed gene, METTL7B, was highly expressed in thyroid cancers. We analyzed METTL7B expression using TCGA and performed qRT-PCR on tissue samples. Moreover, an analysis of clinicopathological characteristics revealed a positive correlation between METTL7B and lymph node metastasis. A series of in vitro experiments indicated that METTL7B enhanced migration and invasion of thyroid carcinoma cells. Further studies revealed that METTL7B may enhance TGF-ß1-induced epithelial-mesenchymal transition (EMT). Our results indicate that METTL7B may promote metastasis of thyroid cancer through EMT and may therefore be considered as a potential biomarker for the diagnosis and prognosis of thyroid carcinoma.

Lipase member H is a downstream molecular target of hypoxia inducible factor-1α and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. MATERIALS AND METHODS: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. RESULTS: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial-mesenchymal transition pathway in PTC. CONCLUSION: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future.

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.

Feasibility and Diagnostic Performance of Voxelwise Computed Diffusion-Weighted Imaging in Breast Cancer.

BACKGROUND: Conventional diffusion-weighted imaging (DWI) with high b-values may improve lesion conspicuity, but with a low signal intensity and thus a low signal-to-noise ratio (SNR). The voxelwise computed DWI (vcDWI) may generate high-quality images with a strong lesion signal and low background. PURPOSE: To evaluate the feasibility and diagnostic performance of vcDWI. STUDY TYPE: Retrospective. POPULATION: In all, 67 patients with 72 lesions, 33 malignant and 39 benign. FIELD STRENGTH/SEQUENCE: 3T, including T2 /T1 , DWI with two b-values, and dynamic contrast-enhanced MRI (DCE-MRI). ASSESSMENT: Computed DWI (cDWI) with high b-values of 1500, 2000, 2500 s/mm2 (cDWI1500 , cDWI2000 , cDWI2500 ) and vcDWI were generated from measured DWI (mDWI). The mDWI, cDWIs and vcDWI were evaluated by three readers independently to determine lesion conspicuity, background signal suppression, overall image quality using 1-5 rating scales, as well as to give BI-RADS scores. The mean apparent diffusion coefficient (ADC) value for each lesion was measured. STATISTICAL TESTS: Agreement among the three readers was evaluated by the intraclass correlation coefficient. Receiver operating characteristic (ROC) analysis was performed to compare the diagnostic performance based on reading of mDWI, cDWIs, vcDWI, and the measured ADC values. RESULTS: vcDWI provided the best lesion conspicuity compared with mDWI and cDWIs (P < 0.005). For overall image quality, vcDWI was significantly better than cDWI (P < 0.005), but not significantly better compared with mDWI for two readers (P = 0.037 and P = 0.013) and significantly worse for the third reader (P < 0.005). Background signal suppression was the best on cDWI2500 , and better on vcDWI than on mDWI, cDWI1500 , and cDWI2000 . The AUC value for differential diagnosis was 0.868 for mDWI, 0.862 for cDWI1500 , 0.781 for cDWI2000 , 0.704 for cDWI2500 , 0.946 for vcDWI, 0.704 for ADC value, and 0.961 for DCE-MRI. DATA CONCLUSION: vcDWI was implemented without increasing scanning time, and it provided excellent lesion conspicuity for detection of breast lesions and assisted in differentiating malignant from benign breast lesions. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Clinicopathological characteristics and prognostic factors for primary thyroid lymphoma: report on 28 Chinese patients and results of a population-based study.

OBJECTIVES: Few studies on prognostic indicators for primary thyroid lymphoma (PTL) have been presented due to the uncommon nature of the tumor. This is the first study to explore the independent prognostic factors in the 2 PTL subtypes. METHODS: We retrospectively reviewed 1,653 cases of PTL. The cases comprised 28 Chinese patients from a local cohort and 1,625 patients from the Surveillance, Epidemiology, and End Results database from 1973 to 2013. Statistical analysis was performed to determine the demographics and prognostic factors of PTL patients. RESULTS: The disease-specific survival (DSS) and prognostic indicators were significantly different between patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and patients with diffuse large B-cell lymphoma (DLBCL). Patients with MALT lymphoma were younger (P=0.011) and had lower clinical stage (P=0.014) compared to patients with DLBCL. Cox regression analysis revealed that age, treatment modalities employed, clinical stage, and number of other types of cancer were independent prognostic factors for DLBCL patients. CONCLUSION: PTL demonstrates specific clinical features and is associated with a relatively good prognosis. Older age is associated with poor DSS in both MALT patients and DLBCL patients. Additionally, combination of different treatment modalities is associated with improved DSS in DLBCL patients.

TEKT4 Promotes Papillary Thyroid Cancer Cell Proliferation, Colony Formation, and Metastasis through Activating PI3K/Akt Pathway.

Thyroid carcinoma is the most common malignancy of the endocrine system worldwide, but its molecular mechanisms remain unclear. Some diseases are associated with TEKT4 gene. However, its role in thyroid carcinoma has yet to be fully examined. This study was designed to investigate the function of TEKT4 in papillary thyroid cancer (PTC). The effect of TEKT4 on aggressive behavior of PTC cell lines, namely, TPC1 and BCPAP, transfected with small interfering RNA was identified through cell proliferation, colony formation, migration, and invasion. Our previous study revealed that TEKT4 may be vital in PTC. In in vitro experiments, TEKT4 downregulation suppressed cell proliferation, colony formation, cell migration, and invasion. Our data also indicated that tumor-suppressing role of TEKT4 knockdown in PTC cell lines was associated with the silence of the PI3K/Akt pathway. Our study revealed that TEKT4 shows important biological implications and is worthy of further study.

Clinical effect of MUC1 and its relevance to BRAF V600E mutation in papillary thyroid carcinoma: a case-control study.

AIM: To investigate the clinical effects of MUC1 on papillary thyroid cancer (PTC) and explore the relationship between MUC1 expression and BRAF mutation. METHODS: The data of 69 patients subjected to fine-needle aspiration biopsy in our hospital and 486 patient data downloaded from The Cancer Genome Atlas (TCGA) database were used. Univariate and multivariate analyses were performed. RESULTS: The results on the 486 patients recorded in the TCGA indicated that high MUC1 expression was independently related to BRAF mutation, lymph node metastasis (LNM), and unifocal type. In the 69 fine-needle aspiration biopsy patients with PTC, high MUC1 expression was significantly related to LNM and extrathyroid extension (ETE). The result of Pearson's correlation coefficient showed that BRAF mutation and MUC1 expression were moderately correlated. Moreover, in the subgroup with low MUC1 expression, the patients with BRAF mutation had higher ETE frequency and LNM than those without BRAF mutation. In the subgroup with BRAF mutation, patients with high MUC1 expression exhibited higher ETE frequency than those with low MUC1 expression, and high MUC1 expression occurred in older patients. In the subgroup with BRAF wild-type mutation, patients with high MUC1 expression had a higher incidence of ETE and LNM than those with low expression. CONCLUSION: We demonstrated that the MUC1 is an important oncogene in PTC and may have great significance on therapeutic cancer vaccine development.

Correlation of Cystatin E/M with Clinicopathological Features and Prognosis in Triple-Negative Breast Cancer.

BACKGROUND: Among all kinds of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive, with the poorest prognosis and highest mortality rates. Thus, novel biomarkers that personalize the therapeutic regimen and evaluate prognosis for TNBC patients should be determined. METHODS: We analyzed the cystatin E/M (CST6) expression profiles of 161 TNBC tissues and 14 noncancerous tissues through multiple statistical analyses. We also investigated the relationship of CST6 expression with clinical parameters and evaluated the prognostic value of CST6 in 161 TNBC patients. RESULTS: CST6, a member of the cystatin superfamily, was remarkably more up-regulated in TNBC tissues than in adjacent normal breast tissues. High CST6 expression was frequently observed in white people and associated with a high risk of lymph-node metastasis. Cox regression analysis confirmed that the high CST6 expression was an independent predictor of disease-free survival in TNBC. Kaplan-Meier analysis further revealed that high CST6 expression caused a low disease-free survival rate. CONCLUSION: CST6 is involved in the progression of TNBC and may act as a tumor-promoter gene. A systematic literature review shows that our study is the first to explore the relationship between CST6 and TNBC.

GABRB2 plays an important role in the lymph node metastasis of papillary thyroid cancer.

BACKGROUND: Thyroid cancer is a common malignant tumor of the endocrine system. Its incidence has increased continuously worldwide for the past three decades. With advanced sequencing technology, we discovered that GABRB2 gene is overexpressed in tumor tissues and closely associated with vertebrate nervous systems. However, its role in cancer remains unclear. METHODS: We conducted a massively parallel whole transcriptome resequencing and a comprehensive analysis of matched papillary thyroid carcinoma (PTC) tumors and normal tissues in 19 patients. Results showed that GABRB2 expression was significantly upregulated in thyroid cancer. Forty-five pairs of tumors and normal tissues were subjected to reverse transcription polymerase chain reaction to validate previous findings. The specific functions of GABRB2 in PTC cell lines (BCPAP, TPC1, and KTC-1) transfected with small interfering RNA were determined through cell colony formation, Cell Counting Kit-8, Transwell migration, Transwell invasion, and apoptosis assays. The effect of DNA demethylation on this gene was also examined. RESULTS: GABRB2 was remarkably overexpressed in primarily sequenced PTC tumors and validation cohort (T: N = 4.94 ± 3.43:0.83 ± 1.71, P < 0.001), and this observation was consistent with that in the TCGA cohort (T: N = 38.92 ± 35.53:0.30 ± 0.55, P < 0.001). GABRB2 overexpression was correlated with lymph node metastasis in both cohorts (P < 0.01). In vitro experiments revealed that GABRB2 downregulation significantly inhibited the colony formation, migration, and invasion of the three PTC cell lines. CONCLUSION: GABRB2 plays important tumorigenic functions and acts as a novel oncogene in PTC.

ZCCHC12, a novel oncogene in papillary thyroid cancer.

PURPOSE: Thyroid cancer is the most common endocrine malignancy worldwide. The molecular mechanisms underlying thyroid tumorigenesis remain unclear. Some studies suggested that the ZCCHC12 gene correlates with certain diseases. However, the function of ZCCHC12 in thyroid cancer has yet to be determined. This study investigated the role of the ZCCHC12 gene in papillary thyroid cancer (PTC). METHODS: We conducted a comprehensive analysis of massively parallel whole-transcriptome resequencing of matched PTC tumors and normal tissues in 19 patients. Results showed that the expression of ZCCHC12 was significantly upregulated in thyroid cancer. qRT-PCR was performed to confirm previous results. The functions of the ZCCHC12 gene in PTC cell lines (TPC1 and BCPAP) transfected with small interfering RNA were determined through cell colony formation assay, migration assay, and invasion assay. RESULTS: The ZCCHC12 gene was remarkably upregulated in primary PTC tumors in both validated cohort (T:N = 1.80 ± 2.58:0.23 ± 0.50, P < 0.01) and TCGA cohort (T:N = 7.63 ± 3.25:1.55 ± 1.71, P < 0.01). We also achieved area under the curve (AUC of ROC) of 87.9% for the validated cohort while 91.4% for the TCGA cohort to classify PTC tumors and normal tissues. ZCCHC12 overexpression correlated with lymph node metastasis in both cohorts (P < 0.05). In in vitro experiments, ZCCHC12 downregulation significantly inhibited the colony formation, migration, and invasion of PTC cells. CONCLUSION: Our study indicated that ZCCHC12 gene has important biological functions and acts as a metastasis-related oncogene in PTC.

Additional Prognostic Value of Lymph Node Ratio (LNR) and Number of Negative Lymph Nodes (NLNs) in Chinese Patients with Triple Negative Breast Cancer.

OBJECTIVE: This study aimed to investigate the prognostic value of lymph node ratio (LNR), number of removed lymph nodes (RLNs), and number of negative lymph nodes (NLNs) in Chinese patients with triple negative breast cancer. METHODS: The study cohort comprised 394 breast cancer patients with the triple negative subtype. The log-rank test and Cox proportional hazards analysis was employed to identify prognostic clinicopathological factors. RESULTS: The median follow-up time was 61 months, and the five-year disease-free survival (DFS) and overall survival (OS) were 63.75% and 64.97%, respectively. Univariate Cox survival analysis revealed that pN stage, LNR, and NLNs were significant prognostic factors for DFS and OS (all, p<0.05). Multivariate analysis including pN stage and LNR showed that LNR was an independent prognostic factor for DFS (p=0.047) and OS (p=0.0497). When combining pN stage, LNR, and NLNs together, only NLNs was an independent prognostic factor for DFS and OS (p=0.014). LNR is prognostically superior to pN stage in patients with triple negative breast cancer. CONCLUSIONS: Our study revealed that LNR and NLNs can provide additional prognostic value for DFS and OS. Moreover, LNR had a better prognostic value compared with pN stage.

Regulator of G protein signaling 20 correlates with clinicopathological features and prognosis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Therefore, finding a novel molecular biomarker for TNBC to achieve target therapy and predict its prognosis is crucial in preventing inappropriate treatment. Regulator of G-protein signaling (RGS) families of protein can negatively regulate signaling of heterotrimeric G proteins and are known to be upregulated in various tumors. In this study, we demonstrated that RGS20 was more highly expressed in TNBC tumor tissue than in adjacent normal tissue by analyzing the cancer genome atlas (TCGA) database. However, RGS20 expression was low in all breast cancer and luminal breast cancer patients. Validated by the TCGA cohort, RGS20 was upregulated in lymph node-positive TNBC compared with that in lymph node-negative breast cancer. High expression of RGS20 had a risk of lymph node metastasis, ki-67 > 14%, poor N stage, and poor clinical stage in the immunohistochemistry of tissue microarrays. Moreover, K-M plot analysis showed that TNBC patients with high RGS20 expression had poor relapse-free survival. In summary, the findings revealed that RGS20 was a special TNBC oncogene that promoted tumor progression and influenced TNBC prognosis. This study is the first to show that RGS20 was a special oncogene, and its high expression was significantly associated with the progression and prognosis of TNBC. RGS20 may be a novel molecular biomarker for the targeted therapy and prognosis of TNBC.

Next-generation sequence detects ARAP3 as a novel oncogene in papillary thyroid carcinoma.

PURPOSE: Thyroid cancer is the most frequent malignancies of the endocrine system, and it has became the fastest growing type of cancer worldwide. Much still remains unknown about the molecular mechanisms of thyroid cancer. Studies have found that some certain relationship between ARAP3 and human cancer. However, the role of ARAP3 in thyroid cancer has not been well explained. This study aimed to investigate the role of ARAP3 gene in papillary thyroid carcinoma. METHODS: Whole exon sequence and whole genome sequence of primary papillary thyroid carcinoma (PTC) samples and matched adjacent normal thyroid tissue samples were performed and then bioinformatics analysis was carried out. PTC cell lines (TPC1, BCPAP, and KTC-1) with transfection of small interfering RNA were used to investigate the functions of ARAP3 gene, including cell proliferation assay, colony formation assay, migration assay, and invasion assay. RESULTS: Using next-generation sequence and bioinformatics analysis, we found ARAP3 genes may play an important role in thyroid cancer. Downregulation of ARAP3 significantly suppressed PTC cell lines (TPC1, BCPAP, and KTC-1), cell proliferation, colony formation, migration, and invasion. CONCLUSION: This study indicated that ARAP3 genes have important biological implications and may act as a potentially drugable target in PTC.