GNPNAT1 is a Biomarker That Predicts a Poor Prognosis of Breast Cancer.

Background: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent. Materials and Methods: The data on gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of GNPNAT1 in 40 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed into six groups, and then the Kaplan-Meier survival analysis with a Log rank test was applied to investigate the involvement among the expression of GNPNAT1 and overall survival (OS). Results: We found higher expression of GNPNAT1 was connected with poor survival in breast cancer by COX regulation analysis. GO, KEGG, and GSEA analysis prompted that GNPNAT1 was connected with the defense mechanism of cells, cell proliferation, and division. Immunization infiltration analysis showed that high GNPNAT1 was negatively connected with 16 immunization infiltration cell types and positively connected with four immunization infiltration cell types. Conclusion: As a whole, our results indicated that GNPNAT1 might be a probable biomarker for diagnosis and prognosis in breast cancer.

Exploring the Oncogenic Potential of TIMM8A: A Crucial Factor in Breast Cancer Tumorigenesis.

BACKGROUND: Female breast cancer has become the world's most common malignant tumor, displacing lung malignancy, and the incidence of malignant tumors has increased continuously in recent decades. However, the underlying molecular mechanisms of breast tumorigenesis have not been fully elucidated. By consulting the literature, we discovered that the TIMM8A gene could affect oxidative stress and apoptosis in patients with Mohr-Tranebjærg syndrome. However, the biological function of TIMM8A has yet to be explored. MATERIALS AND METHODS: We investigated the expression level of TIMM8A via bioinformatic analysis and performed immunohistochemistry, diagnostic value, immune infiltration, functional enrichment, and survival analyses. Nonetheless, in vitro, additional experiments were performed. We explored whether TIMM8A expression was greater in breast tumors than in nearby normal tissues through qRT‒PCR. The expression of TIMM8A was knocked down by siRNA. Then, we conducted proliferation tests (CCK-8 experiment and colony formation) and Transwell assays (migration and invasion assays) to determine the specific biological functions of TIMM8A in the MDA-MB-231 and BT-549 cell lines. RESULTS: Tumor samples exhibited higher TIMM8A expression and exon expression, whereas normal tissues had higher TIMM8A methylation. The expression level of TIMM8A was linked to immune infiltration and survival, making it a valuable prognostic indicator and effective diagnostic tool. Functional enrichment analysis of TIMM8A indicated potential pathways through which it may play a role. In vitro experiments demonstrated that suppressing TIMM8A significantly inhibited the viability, colony formation, migration, and invasion of breast carcinoma cell lines. CONCLUSION: This study revealed that TIMM8A is an oncogene and is critical for the tumorigenesis of breast carcinoma.

Serine Protease 27, a Prognostic Biomarker in Pan-cancer and Associated with the Aggressive Progression of Breast Cancer.

BACKGROUND: To create effective medicines, researchers must first identify the common or unique genes that drive oncogenic processes in human cancers. Serine protease 27 (PRSS27) has been recently defined as a possible driver gene in esophageal squamous cell carcinoma. However, no thorough pan-cancer study has been performed to date, including breast cancer. METHODS: Using the TCGA (The Cancer Genome Atlas), the GEO (Gene Expression Omnibus) dataset, and multiple bioinformatic tools, we investigated the function of PRSS27 in 33 tumor types. In addition, prognosis analysis of PRSS27 in breast cancer was carried out, as well as in vitro experiments to verify its role as an oncogene. We first explored the expression of PRSS27 in over 10 tumors and then we looked into PRSS27 genomic mutations. RESULTS: We discovered that PRSS27 has prognostic significance in breast cancer and other cancers' survival, and we developed a breast cancer prognostic prediction model by combining a defined set of clinical factors. Besides, we confirmed PRSS27 as an oncogene in breast cancer using some primary in vitro experiments. CONCLUSION: Our pan-cancer survey has comprehensively reviewed the oncogenic function of PRSS27 in various human malignancies, suggesting that it may be a promising prognostic biomarker and tumor therapeutic target in breast cancer.

Monocyte-to-High-Density Lipoprotein Cholesterol Ratio Together With the Lymphocyte-to-Monocyte Ratio in Predicting the Malignancy of the Thyroid Nodule in Patients Complicated With Type 2 Diabetes.

Background: Thyroid nodules, although mostly benign and symptomless, have a small chance of being cancerous, necessitating accurate diagnosis. This study aims to develop and validate a nomogram for differentiating malignant and non-malignant thyroid nodules in individuals with type 2 diabetes. Methods: The study included 484 patients with both thyroid nodules and type 2 diabetes who underwent thyroid gland lobectomy at Wenzhou Medical University Hospital. Optimal cutoff values for continuous variables were determined using ROC curve analysis. Significant factors identified in univariable analysis were used to construct the nomogram. The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) was visualized through a histogram and scatter diagram. Discriminatory power was assessed using ROC analysis, and calibration curves ensured consistency. Decision curve analysis (DCA) evaluated clinical benefits. Results: The cohort was divided into a training group (70%) and an internal validation group (30%). The scatter diagram revealed a correlation between MHR levels and the proportion of goiter cases, with higher MHR levels associated with increased goiter incidence. The histogram showed higher average MHR levels in goiter patients compared to those with papillary thyroid carcinoma (PTC) in both groups. Multivariate logistic regression identified age, total cholesterol (TC), triglyceride (TG), fasting blood sugar (FSG), fibrinogen, lymphocyte-to-monocyte ratio (LMR), and MHR as independent predictive factors for malignancy in thyroid nodules with type 2 diabetes. The nomogram achieved high discrimination, with C-index values of 0.901 (training data set) and 0.760 (internal validation data set). Calibration curves displayed good agreement, and DCA demonstrated significant net clinical benefits. Conclusions: MHR is associated with sex, serum cholesterol levels, and peripheral blood cell counts, making it a potential novel biomarker for differentiating between PTC and goiter in type 2 diabetes patients.

LINC00891 promotes tumorigenesis and metastasis of thyroid cancer by regulating SMAD2/3 via EZH2.

BACKGROUND: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays. METHODS: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion apoptosis, and of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting. RESULTS: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown. CONCLUSION: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

Budding uninhibited by benzimidazoles 1 might be a poor prognosis biomarker promoting the progression of papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most widespread malignant tumors of the endocrine system, with a high incidence. Budding uninhibited by benzimidazoles 1 (BUB1), one of the spindle assembly checkpoint (SAC) genes, is a multitask protein kinase required for eukaryotic chromosome segregation. Although BUB1 has been explored in several types of cancer, its biological role and molecular mechanisms in PTC remain unclear. METHODS: In this study, we performed an examination of four public datasets along with local PTC cohorts and discovered that BUB1 was elevated in PTC compared to non-cancer tissues. High BUB1 expression was linked with the status of BRAFV600E , RAS, and TERT after statistical analysis. RESULTS: Clinically, BUB1 is associated with a variety of clinicopathological features in PTC patients. Interestingly, analysis of the TCGA database showed that BUB1 was closely associated with poor prognosis of PTC and significantly correlated with PFS. As determined by regression analysis, BUB1, and T stage were independent predictors of PTC and were related to BRAFV600E and lymph node metastatic status. By RT-qPCR, BUB1 was considerably overexpressed in PTC cell lines in comparison with normal thyroid epithelial cells. CONCLUSION: We confirmed that the knockdown of BUB1 in BCPAP and TPC1 cell lines significantly inhibited cell proliferation, cloning, and migration in vitro experiments. These results imply that BUB1 may be a significant oncogenic gene that is directly associated with the prognosis of PTC and may represent a future target for therapeutic intervention.

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.

The pan-cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target.

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

S100A6 promotes the development of thyroid cancer and inhibits apoptosis of thyroid cancer cells through the PI3K/AKT/mTOR pathway.

High levels of S100A6 have been associated with progression in some types of human cancers. Cancers related to S100A6 have been reported to include lung cancer, cervical cancer, pancreatic cancer, gastric cancer, colon cancer, etc., but its role in the molecular pathogenesis of these cancers is largely unknown. This study investigated the expression and functional roles of S100A6 in human thyroid cancer. The expression level of S100A6 in thyroid cancer cells was determined by bioinformatics and transcriptomic analysis. Furthermore, the potential functions of S100A6 in tumorigenesis were analyzed by cell proliferation, migration, invasion, and Western blot assays in human thyroid cancer cells. Public database queries revealed high S100A6 expression in thyroid cancer. In addition, we also found that high expression of S100A6 was positively correlated with malignant clinicopathological characteristics of thyroid cancer in The Cancer Genome Atlas database. qPCR results confirmed the high expression of S100A6 in thyroid cancer cells. S100A6 silencing inhibited cell proliferation, migration, and invasion. Western blot assays and response experiments showed that S100A6 promotes cell proliferation and tumorigenicity partly through the PI3K/AKT/mTOR signaling pathway. These results suggest that S100A6 affects the progression of thyroid cancer and can be used as a target in the future treatment of thyroid cancer.

PDZK1IP1 gene promotes proliferation, migration, and invasion in papillary thyroid carcinoma.

Thyroid cancer is a common malignant tumor for the adult and the potential molecular mechanism of papillary thyroid cancer cell metastasis is still unclear. We used sequencing techniques to analyze paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissue and identified a gene, PDZK1IP1, that was significantly overexpressed in thyroid cancer. We found It has been detected to play an important role in many malignant tumors. But the role in papillary thyroid cancer was still unknown, we decided to find a new marker and therapeutic target for the disease. The present study shows that PDZK1IP1 may be a potential gene that leads to thyroid cancer. In our study, silencing PDZK1IP1 can inhibit PTC cell proliferation, migration, invasion, apoptosis, and cell cycle arrest. This study surmised that PDZK1IP1 was an oncogene that correlated with tumor development.

AHNAK2 promotes the progression of differentiated thyroid cancer through PI3K/AKT signaling pathway.

AIMS: AHNAK2 may be used as a candidate marker for TC diagnosis and treatment. BACKGROUND: Thyroid cancer [TC] is the most frequent malignancy in endocrine carcinoma, and the incidence has been increasing for decades. OBJECTIVE: To understand the molecular mechanism of DTC, we performed next-generation sequencing [NGS] on 79 paired DTC tissues and normal thyroid tissues. The RNA-sequencing [RNA-seq] data analysis results indicated that AHNAK nucleoprotein 2 [AHNAK2] was significantly upregulated in the thyroid cancer patient's tissue. METHOD: We also analyzed AHNAK2 mRNA levels of DTC tissues and normal tissues from The Cancer Genome Atlas [TCGA]. The association between the expression level of AHNAK2 and clinicopathological features was evaluated in the TCGA cohort. Furthermore, AHNAK2 gene expression was analyzed by quantitative real-time polymerase chain reaction [qRT-PCR] in 40 paired DTC tissues and adjacent normal thyroid tissues. The receiver operating characteristic [ROC] curve was performed to evaluate the diagnostic value of AHNAK2. For cell experiments in vitro, AHNAK2 was knocked down using small interfering RNA [siRNA], and the biological function of AHNAK2 in TC cell lines was investigated. The expression of AHNAK2 was significantly upregulated in both the TCGA cohort and the local cohort. RESULT: The analysis results of the TCGA cohort indicated that the upregulation of AHNAK2 was associated with tumor size [P<0.001], lymph node metastasis [P<0.001], and disease stage [P<0.001]. The area under the curve [AUC] [TCGA: P<0.0001; local validated cohort: P<0.0001.] in the ROC curve revealed that AHNAK2 might be considered a diagnostic biomarker for TC. The knockdown of AHNAK2 reduced TC cell proliferation, colony formation, migration, invasion, cell cycle, and induced cell apoptosis. CONCLUSION: Furthermore, the protein levels of phospho-PI3 Kinase p85 and phospho-AKT were down-regulated in the transfected TC cell. Our study results indicate that AHNAK2 may promote metastasis and proliferation of thyroid cancer through PI3K/AKT signaling pathway. Thus, AHNAK2 may be used as a candidate marker for TC diagnosis and treatment.

Overexpression of galectin2 (LGALS2) predicts a better prognosis in human breast cancer.

BACKGROUND: Galectins (LGALS) are a family of carbohydrate-binding proteins, and LGALS family members have shown prognostic roles in various types of cancers. However, the prognostic significance of some LGALS family members has not been studied in breast malignancy. METHODS: The prognostic value of LGALS family mRNA expression in breast cancer patients was investigated according to distinct clinicopathological features (including lymph node, intrinsic subtype, pathological grade, HER2, and TP53 status) using the Kaplan-Meier plotter database. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression of LGALS in breast cancer and normal breast cells. The aberrant expression of specific LGALS and its correlation with breast cancer outcomes remains elusive. In the present analysis, we comprehensively explored an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer, and cell lines from the widely available Human Protein Atlas (HPA) database. Immunohistochemistry was applied to evaluate the expression of LGALS between cancer and normal tissues. RESULTS: Our results showed that overexpression of LGALS2 mRNA were correlated with satisfactory overall survival among all breast cancer patients. Furthermore, LGALS2 and LGALS4 expression correlated with a better overall survival (OS) in grade III breast cancer patients; LGALS2 also predicted a better OS in basal-like subtype patients, luminal B patients, HER2-overexpressing patients, TP53 mutated and wild breast cancer patients. Notably, the mRNA and protein expression levels of LGALS2 were decreased in cancer cells compared with normal cells (P<0.05). Furthermore, LGALS2 expression in immunostaining score was lower in cancer tissues than in normal tissues (P<0.005). CONCLUSION: In conclusion, LGALS2 has potential as a valuable biomarker for envisaging a satisfactory prognosis in patients with breast tumours, particularly those with luminal and basal B types, all stages and grade III tumours.

Prognostic role of overexpressed Bromodomain and extra-terminal family in ovarian cancer.

Background: BET family proteins have a role as epigenetic readers to accelerate the transcription of target genes. Several studies have shown that the BET protein family played important roles in several biological processes. Although, the prognostic influence of individual BET genes family in ovarian cancer patients remains unclear. Methods: We investigated BET mRNA prognostic roles subtypes in ovarian cancer patients by means of the KM plotter database. The BET mRNA expression and protein in cancer and normal ovarian cells was determined using qRTPCR and western blot. We used the HPA database to look at the protein expression profiles in normal and cancer tissues for this study. Results: Among BET members, mRNA expression BRD2 showed improve OS in all the ovarian malignancy patients, serous patients, stage III and IV, grade II and grade III, TP53 mutated ovarian cancer patients, as well as all patients treated with Platin based chemotherapy. As for BRD3, we found that BRD3 expression was related to better OS in endometrioid ovarian carcinoma and stage III+IV ovarian carcinoma patients, as well as all patients managed with Taxol and concurrent Taxol+Platin based chemotherapy. In addition, BRDT was associated with better OS in all ovarian carcinoma patients, grade I and grade III, all clinical stage (I+II, III+IV) patients, as well as all patients cured with Taxol and concurrent Taxol+Platin chemotherapy. Conclusion: We conclude that high expression of BRD2, BRD3, and BRDT predicted a better prognosis. mRNA expression of BET family is considerably associated with the prognosis of ovarian carcinoma and individual BET family gene could act as a predictive prognostic indicator in ovarian carcinoma.

Erratum: Long non-coding RNA LINC00673 promotes breast cancer proliferation and metastasis through regulating B7-H6 and epithelial-mesenchymal transition.

[This corrects the article on p. 1273 in vol. 8, PMID: 30094100.].

SEC61G regulates breast cancer cell proliferation and metastasis by affecting the Epithelial-Mesenchymal Transition.

Breast cancer is a common malignant tumor for women and its incidence has increased constantly in recent decades. The underlying molecular means of breast tumorigenesis endure uncertain. With the sequencing expertise, we found that the SEC61G gene is overexpressed in tumor tissues. However, the biological function of SEC61G in breast malignancy has yet to be determined. We investigated the SEC61G expression level, genetic alteration, IHC, immune infiltration, diagnostic value, survival analysis, and functional enrichment analysis by bioinformatics analysis. Then, vitro experiments were done. We investigated that SEC61G was greater in breast cancer tissues related to adjacent non-tumor tissues through qRT-PCR. We performed proliferation, colony formation, migration, invasion assays, and EMT-related phenotype to determine the specific biological functions of SEC61G in breast cancer cell lines (MDA-MB-231, BT-549) transfected with small interfering RNA. SEC61G expression and exon expression were higher in the tumor while the level of SEC61G methylation was higher in normal tissues. The expression level of SEC61G was connected with immune infiltration and survival and was an effective diagnostic and prognostic indicator. The functional enrichment analysis of SEC61G prompted that SEC61G might play a tumor-promoting role via the EMT pathway. In vitro experiments indicated that knocking down SEC61G considerably impaired the colony formation, cck-8, migration, and invasion, and induced apoptosis of the breast cancer cell lines. The vitro experiments also indicated that ectopic expression of SEC61G could influence EMT. This study revealed that SEC61G plays vital tumorigenic functions and acts as a novel oncogene in breast cancer.

The ETNK2 gene promotes progression of papillary thyroid carcinoma through the HIPPO pathway.

Thyroid cancer is a disease with an extremely high incidence rate and is divided into papillary, follicular, medullary, and undifferentiated thyroid cancers. Among them, papillary carcinoma is the most common subtype. We assessed expression of ETNK2 in public databases and found that ETNK2 is upregulated in PTC. Cohort and RNA sequencing data were used to verify this discovery. To further determine the relationship between ETNK2 and papillary thyroid carcinoma, we performed an in vitro experiment. In a PTC cell line, silencing ETNK2 inhibited cell proliferation, weakened cell migration and invasion ability, promoted apoptosis, and blocked the cell cycle. In addition, western blotting suggested that ETNK2 is related to the HIPPO pathway and may activate the EMT pathway through the HIPPO pathway to promote the development of thyroid cancer. These results revealed that ETNK2 is related to the occurrence and development of papillary thyroid carcinoma, suggesting that ETNK2 may be an oncogene associated with PTC.

ErbB inhibitors as neoadjuvant therapy for triple-positive breast cancer: a network meta-analysis.

BACKGROUND: Evidence on the effectiveness of ErbB inhibitor interventions for women with triple-positive breast cancer (TPBC) is scarce. Exposure to hormone receptors was reported to eclipse targeted intervention effectiveness. Here, we aimed to explore the optimum targeted regimen for TPBC. METHODS: We conducted a thorough search of the literature focusing on neoadjuvant targeted therapy with both hormone receptor-positive and HER2 (ErbB2)-positive patients and performed a network meta-analysis comparing the regimens using a random-effects model. The rate of pathological complete response (pCR) (ypT0/is) was the primary outcome. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association among twelve regimens. RESULTS: Thirteen studies meeting the inclusion criteria were included. Significantly more TPBC patients receiving ado-trastuzumab emtansine plus lapatinib experienced pCR events than other patients. In the high-performance ranking of the twelve regimens, ado-trastuzumab emtansine plus lapatinib (TDM-1+L) ranked top, followed by ado-trastuzumab emtansine (TDM-1), trastuzumab plus carboplatin, taxanes and pertuzumab (TCHP), trastuzumab plus docetaxel and lapatinib (THL), trastuzumab, taxanes and pertuzumab (THP), ado-trastuzumab emtansine plus pertuzumab (TDM1+P), trastuzumab plus taxanes (TH), trastuzumab plus taxanes and neratinib, taxanes plus pertuzumab (HP), taxanes and neratinib (HN), trastuzumab plus lapatinib (TL), trastuzumab plus pertuzumab (TP) in sequence. CONCLUSION: Double-targeted therapy in chemotherapy-based regimens was associated with better pCR than single-targeted therapy, and TDM-1+L stood out. For either single-targeted or double-targeted therapies, regimens free of chemotherapy were always worse than those with targeted therapy. Our data support guidelines that recommend combinations of chemotherapies plus targeted therapies in the neoadjuvant setting for early TPBC.

SYT12 is a novel oncogene that promotes thyroid carcinoma progression and metastasis.

Background: Thyroid malignancy is the most frequent endocrine malignant tumor whose incidence is still increasing. Mechanisms genomic variations play a major part in the pathogenesis of many types of malignancy. Synaptotagmin 12 (SYT12) is a member gene of the synaptotagmins family and SYT12's variants were shown to be associated with some malignancies. Nevertheless, SYT12's specific function and probable clinical value in papillary cancer were still unknown. Methods: We conducted complete genome sequence of 39 pairs PTC malignant neoplasm and matched non-neoplastic tissues. We found that SYT12 was significantly overexpressed in thyroid malignancy. Next, we investigated the expression level of SYT12 and the relation between clinical information and SYT12 expression in thyroid cancer in the Cancer Genome Atlas (TCGA). QRt-PCR of else 40 pairs local verified cohort was performed to confirm the sequencing data and TCGA cohort. Then, we used small interfering RNA (si-RNA) to knock down the expression of SYT12 in PTC cells. Finally, proliferation, cell colony formation, migration, invasion, and apoptosis assays were done to demonstrate the function of SYT12. Results: SYT12 is significantly overexpressed and higher expression of SYT12 upsurges the risk of lymph node metastatic and incidence rate of primary neoplasm multivariate focus type and classical histological type for PTC patients in TCGA cohort. In vitro experiments, the results of functional assays presented that knock-down of SYT12 inhibited the cell proliferation, cell colony formation, trans-well migration, and trans-well invasion and promoted cell apoptotic in PTC cell lines. Conclusion: SYT12 was a novel oncogene that promotes thyroid carcinoma progression and metastasis potential and a potential biomarker for diagnosis and treatment in PTC.

Construction and Analysis of a Colorectal Cancer Prognostic Model Based on N6-Methyladenosine-Related lncRNAs.

Given the relatively poor understanding of the expression and functional effects of the N6-methyladenosine (m6A) RNA methylation on colorectal cancer (CRC), we attempted to measure its prognostic value and clinical significance. We comprehensively screened 37 m6A-related prognostic long non-coding RNAs (lncRNAs) with significant differences in expression based on 21 acknowledged regulators of m6A modification and data on 473 colorectal cancer tissues and 41 para-cancer tissues obtained from the TCGA database. Accordingly, we classified 473 CRC patients into two clusters by consensus clustering on the basis of significantly different survival outcomes. We also found a potential correlation between m6A-related prognostic lncRNAs and BRAF-KRAS expression, as well as immune cell infiltration. Then, we established a prognostic model by selecting 16 m6A-related prognostic lncRNAs via LASSO Cox analysis and grouped the CRC patients into low- and high-risk groups to calculate risk scores. Then, we performed stratified sampling to validate and confirm our model by categorising the 473 samples into a training group (N = 208) and a testing group (N = 205) in a 1:1 ratio. The survival curve showed a distinct clinical outcome in the low- and high-risk subgroups. We reconfirmed the reliability and independence of the prognostic model through various measures: risk curve, heat map and univariate and multivariate Cox analyses. To ensure that the outcomes were applicable to clinical settings, we performed stratified analyses on different clinical features, such as age, lymph node status and clinical stage. CRC patients with downregulated m6A-related gene expression, lower immune score, distant metastasis, lymph node metastasis or more advanced clinical staging had higher risk scores, indicating less-desirable outcomes. Moreover, we explored the immunology of colorectal cancer cells. The risk score showed positive correlations with eosinophils, M2 macrophages and neutrophils. In summary, our effort revealed the significance of m6A RNA methylation regulators in colorectal cancer, and the prognostic model we constructed may be used as an essential reference for predicting the outcome of CRC patients.

PSD3 is an oncogene that promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in papillary thyroid cancer.

Background: The morbidity of thyroid cancer is gradually increasing, meanwhile, the average age of the morbidity population also becomes younger. Mechanisms genomic variations serve an important function for the pathogenesis of many cancer types. Pleckstrin and sec7 domain-containing 3 (PSD3), also known as EFA6R, was shown to be associated with some cancers such as acute myeloid leukemia, breast cancer metastasis, and astrocytoma. But it was unknown that whether PSD3 took effect and how did it work in thyroid cancer. Methods: We guessed that PSD3 might play an important role in thyroid cancer by consulting previous literature. Then, we analyzed the level of PSD3 expression in thyroid malignancy and the connection with clinical manifestation in The Cancer Genome Atlas (TCGA). And RNA extraction, reverse transcription, and real-time quantitative polymerase chain reaction (qRt-PCR) of 40 pairs of local samples were done to verify the result of TCGA. Then, PSD3 was knocked down by small interfering RNA (siRNA) for flowing functional experiments. Results: Bioinformatics and qRt-PCR analysis shown PSD3 was overexpressed in papillary thyroid cancer (PTC) and connected with the histological type (P=0.009) and risk of lymph node metastasis (P=0.016). In vitro assays, we confirmed that down-regulation PSD3 could not only suppress the cell proliferation, colony formation, cell migration, cell invasion, and G1/S cell cycle transition but also promote apoptosis in PTC cells. Conclusion: PSD3 promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in PTC and a possible biomarker in PTC.