Clinical Efficacy of Neoadjuvant Chemotherapy plus Modified Radical Mastectomy for Stage II-III Breast Cancer Patients and Its Influence on Serum Tumor Markers.

Objective: This research aims to assess the clinical efficacy of neoadjuvant chemotherapy (NACT) in combination with modified radical mastectomy (MRM) for stage II-III breast cancer (BC) patients and its impact on serum tumor markers (STMs). Methods: The study included 119 stage II-III BC patients treated between June 2018 and June 2021. Among them, 55 cases underwent MRM (reference group), while 64 cases received NACT followed by MRM (research group). We compared intraoperative parameters (blood loss, operation time, hospital stay), clinical outcomes, the incidence of postoperative adverse events (AEs), changes in STMs (CA125, CA153, CEA), and one-year postoperative quality of life (QOL). Results: In comparison to the reference group, the research group exhibited significantly lower intraoperative blood loss, shorter operation times, reduced hospital stays, and higher rates of disease remission. Notably, the research group experienced a lower overall incidence of AEs, including skin flap necrosis, subscalp effusion, infection, and upper limb lymphedema. Postoperatively, all STMs in the research group exhibited statistically significant reductions and were lower than those in the reference group. Additionally, all QOL subscales demonstrated improvements and higher scores in the research group. Conclusions: NACT followed by MRM represents an effective approach for enhancing surgical outcomes and clinical efficacy in stage II-III BC patients. This combination therapy also reduces the risk of postoperative AEs and leads to favorable changes in STMs and postoperative QOL levels.

Causal effects of genetically predicted endometriosis on breast cancer: a two-sample Mendelian randomization study.

This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90-0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86-0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94-1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association.

Artificial intelligence in breast cancer: application and future perspectives.

Breast cancer is one of the most common cancers and is one of the leading causes of cancer-related deaths in women worldwide. Early diagnosis and treatment are the key for a favorable prognosis. The application of artificial intelligence technology in the medical field is increasingly extensive, including image analysis, automated diagnosis, intelligent pharmaceutical system, personalized treatment and so on. AI-based breast cancer imaging, pathology and adjuvant therapy technology cannot only reduce the workload of clinicians, but also continuously improve the accuracy and sensitivity of breast cancer diagnosis and treatment. This paper reviews the application of AI in breast cancer, as well as looks ahead and poses challenges to the future development of AI for breast cancer detection and therapeutic, so as to provide ideas for future research.

m6A Modification Mediates Exosomal LINC00657 to Trigger Breast Cancer Progression Via Inducing Macrophage M2 Polarization.

BACKGROUND: Exosome-mediated transfer of long noncoding RNAs (lncRNAs) is critical for the cell-cell crosstalk in the tumor microenvironment. Nevertheless, the role of breast cancer (BC) cell-derived exosomal lncRNA in macrophage polarization during the development of BC remains unclear. METHODS: The key lncRNAs carried by BC cell-derived exosomes were identified by RNA-seq. CCK-8, flow cytometry, and transwell assay were conducted to analyze the role of LINC00657 in BC cells. In addition, immunofluorescence, qRT-PCR, western blot, and MeRIP-PCR were used to evaluate the function and underlying mechanism of exosomal LINC00657 in macrophage polarization. RESULTS: LINC00657 was distinctly upregulated in BC-derived exosomes and it was associated with increased m6A methylation modification levels. In addition, the depletion of LINC00657 significantly diminished the proliferative activity, migration and invasion potential of BC cells, and it also accelerated cell apoptosis. Exosomal LINC00657 from MDA-MB-231 cells could facilitate macrophage M2 activation, thus stimulating BC development in turn. Furthermore, LINC00657 activated the TGF-ß signaling pathway by sequestering miR-92b-3p in macrophages. CONCLUSION: Exosomal LINC00657 secreted by BC cells could induce macrophage M2 activation, and these macrophages preferentially contributed to the malignant phenotype of BC cells. These results improve our understanding of BC and suggest a new therapeutic strategy for patients with BC.

"Elastic stretch cavity building" system in endoscopic thyroidectomy via the axillary approach: a case series.

Background: Patients undergoing conventional endoscopic thyroidectomy via the axillary approach, which is commonly used clinically, suffered from a range of postoperative complications. This study aimed to prevent postoperative complications and evaluate patients' satisfaction with cosmetic outcomes in endoscopic thyroidectomy via the axillary with the use of "Elastic Stretch Cavity Building" System. Methods: In this retrospective case series study, the clinical data of patients who were admitted to the Thyroid Surgery Department of Ningbo Medical Centre Lihuili Hospital between December 2020 and December 2021 for endoscopic thyroidectomy via the axillary approach under the "Elastic Stretch Cavity Building" System. Results: A total of 67 patients were included, all surgeries were successfully completed. The operation time was 75.61 ± 13.67 minutes; the postoperative drainage volume was 109.97 ± 37.54 ml; the average postoperative hospital stay was 4 (2-6) days. There was no skin ecchymosis, effusion or infection, hypocalcemia, convulsions, upper extremity dyskinesia, and temporary hoarseness after the surgery. The patients were satisfied with the cosmetic effects, and the cosmetic score was 4 (3-4). Conclusion: The "Elastic Stretch Cavity Building" System in endoscopic thyroid surgery via the axillary approach might reduce the risks of complications and achieve satisfactory results with the cosmetic outcomes.

Hsa_circ_0000129 drives tumor growth via sequestering miR-485-3p and upregulating SPIN1 in breast cancer.

BACKGROUND: Breast cancer (BC) is second cancer frequently occurring worldwide. Circular RNA hsa_circ_0000129 (circ_0000129) exerts a tumor-promoting effect in BC. Nevertheless, the molecular mechanisms mediated by the upregulation of circ_0000129 during BC progression are not well understood. METHODS: Forty-five BC patients were recruited for the research. Changes in circ_0000129 levels were detected with quantitative reverse transcription-polymerase chain reaction. Cell proliferation, apoptosis, migration, invasion, and angiopoiesis were determined by cell counting, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Protein levels were detected by western blot analysis. The regulatory mechanism of circ_0000129 was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo experiments were carried out to verify the function of circ_0000129. RESULTS: Circ_0000129 was overexpressed in BC samples and cell lines. Functionally, circ_0000129 silencing reduced cell proliferation, migration, invasion, and promoted cell apoptosis, as well as induced HUVEC angiopoiesis in vitro. Furthermore, circ_0000129 knockdown decreased BC cell growth in mouse xenograft models. Mechanically, circ_0000129 interacted with miR-485-3p to mediate the inhibiting effect of miR-485-3p on SPIN1. Silenced miR-485-3p expression weakened the inhibiting effect of circ_0000129 knockdown on BC cell malignant behaviors. Also, forced SPIN1 expression weakened miR-485-3p upregulation mediated effects on BC cell malignant behaviors. CONCLUSION: Circ_0000129 acted as a miR-485-3p sponge molecular to mediate expression, thus promoting BC progression.

"Elastic Stretch Cavity Building" System in Endoscopic Thyroidectomy of Giant Thyroid Tumors.

Objective: To analyze the clinical characteristics of patients with large thyroid tumors underwent endoscopic thyroidectomy using the "elastic stretch cavity builder" system. Methods: This retrospective case series study included thyroid tumor patients admitted to the Ningbo Medical Center Li Hui li Hospital between September 2017 and November 2021. The self-developed "elastic stretch cavity builder" was used to elastically lift the anterior cervical flap, combined with low-pressure (3 mmHg) high-flow CO2 inflation, and create a working cavity for endoscopic thyroidectomy. Results: This study included 13 patients for analysis. The endoscopic thyroidectomy duration was 92-170 min (mean, 123 ± 24min). The maximum transverse plane diameter of the glands was 5.0-6.2 cm (mean, 5.3 ± 0.3 cm). The maximum sagittal plane diameter was 6.8-10.0 cm (mean, 7.6 ± 0.9 cm). After the "elastic stretch cavity builder" lifted the cervical flap, the height of the subcutaneous region was increased by 1.3 ± 0.2cm without affecting cervical activity. There was no residual scar in the anterior cervical skin puncture hole. All patients were satisfied with the cosmetic with the cosmetic satisfaction score was 3.4 ± 0.5. Conclusion: The novel mixed cavity building model established by the "elastic stretch cavity builder" might provide the surgeon with additional longitudinal cervical operating space while improving the stability of the space and saving human effort.

Role of lncRNA AGAP2-AS1 in Breast Cancer Cell Resistance to Apoptosis by the Regulation of MTA1 Promoter Activity.

Introduction Breast cancer (BC) is a common malignant tumor affecting women across the world. LncRNAs are frequently implicated in the course of BC. The current study set out to determine the specific effect of lncRNA AGAP2-AS1 on BC cell resistance to apoptosis. Methods AGAP2-AS1 expression patterns in BC tissues and cells were evaluated. si-AGAP2-AS1 was transfected into MCF-7 cells, followed by the assessment of cell proliferation and apoptosis. In addition to detection of MTA1 expression patterns, the binding relation between AGAP2-AS1 and HuR was verified using RNA pull-down and RNA immunoprecipitation. Next, the regulation enrichment of AGAP2-AS1- and HuR to H3K27ac recruitment in the MTA1 promoter was analyzed. MCF-7 cell resistance to apoptosis was observed after the combined experiment of histone deacetylase inhibitor M344 and si-AGAP2-AS1. Lastly, xenografts tumors were established to detect tumor weight and volume, tumor apoptosis and growth as well as expression of AGAP2-AS1 and MTA1. Results AGAP2-AS1 was overexpressed in BC tissues and cells, and AGAP2-AS1 silencing inhibited cell proliferation but facilitated apoptosis. Physiologically, AGAP2-AS1 bound to HuR to stabilize its own expression, and AGAP2-AS1-HuR complex upregulated H3K27ac levels in the MTA1 promoter region to elevate MTA1 promoter activity and MTA1 expression. H3K27ac upregulation partially-annulled the promotive effect of si-AGAP2-AS1 on BC apoptosis by upregulating MTA1. si-AGAP2-AS1 in vivo inhibited MTA1 expression to enhance apoptosis and suppress tumor growth. Conclusion Collectively, our findings indicated that AGAP2-AS1 bound to HuR to stabilize its own expression, and AGAP2-AS1-HuR complex enhanced H3K27ac levels in the MTA1 promoter region to improve MTA1 promoter activity and MTA1 expression in BC cells, so as to augment BC cell resistance to apoptosis.

Validation of the Prognostic Stage from the American Joint Committee on Cancer 8th Staging Manual in Luminal B-Like Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PURPOSE: The 8th edition American Joint Committee on Cancer (AJCC) prognostic staging system (PS) has been validated numerous times; however, the prognostic value of PS for breast cancer based on molecular subtype has rarely been explored. This study aimed to investigate the prognostic value of PS in Chinese patients with luminal B-like human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: A total of 407 eligible cases were included in the study. All of the cases were restaged using the 8th edition AJCC Anatomic Staging System (AS) and PS. The Kaplan-Meier method was used to calculate estimated survival and the Log rank test was used to compare the survival differences between groups. RESULTS: The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 90.3% and 93.5%, respectively, and there were statistically significant differences in the 5-year DSS and 5-year OS rates among the different anatomic and prognostic stage groups. The application of the PS resulted in the assignment of 215 (52.8%) patients to a different group. Different prognostic stage groups restaged from anatomic Stage III had significant differences in both DSS (χ 2 = 4.366, p = 0.037) and OS (χ 2 = 7.549, p = 0.006); additionally, different prognostic stage groups from the anatomic Stage II group had significant differences in DSS (χ 2 = 7.724, p = 0.021) but no significant differences in OS (χ 2 = 5.182, p = 0.075). However, different prognostic stage groups from anatomic Stage I had no significant differences in either DSS (χ 2= 0.159, p = 0.690) or OS (χ 2 = 0.099, p = 0.753). CONCLUSION: The 8th edition AJCC PS refined the anatomic stage grouping in luminal B-like HER2-negative breast cancer and could lead to a more personalized approach to breast cancer treatment.

An autophagy-related long non-coding RNA prognostic model and related immune research for female breast cancer.

Introduction: Breast cancer (BRCA) is the most common malignancy among women worldwide. It was widely accepted that autophagy and the tumor immune microenvironment play an important role in the biological process of BRCA. Long non-coding RNAs (lncRNAs), as vital regulatory molecules, are involved in the occurrence and development of BRCA. The aim of this study was to assess the prognosis of BRCA by constructing an autophagy-related lncRNA (ARlncRNA) prognostic model and to provide individualized guidance for the treatment of BRCA. Methods: The clinical data and transcriptome data of patients with BRCA were acquired from the Cancer Genome Atlas database (TCGA), and autophagy-related genes were obtained from the human autophagy database (HADb). ARlncRNAs were identified by conducting co­expression analysis. Univariate and multivariate Cox regression analysis were performed to construct an ARlncRNA prognostic model. The prognostic model was evaluated by Kaplan-Meier survival analysis, plotting risk curve, Independent prognostic analysis, clinical correlation analysis and plotting ROC curves. Finally, the tumor immune microenvironment of the prognostic model was studied. Results: 10 ARlncRNAs(AC090912.1, LINC01871, AL358472.3, AL122010.1, SEMA3B-AS1, BAIAP2-DT, MAPT-AS1, DNAH10OS, AC015819.1, AC090198.1) were included in the model. Kaplan-Meier survival analysis of the prognostic model showed that the overall survival(OS) of the low-risk group was significantly better than that of the high-risk group (p< 0.001). Multivariate Cox regression analyses suggested that the prognostic model was an independent prognostic factor for BRCA (HR = 1.788, CI = 1.534-2.084, p < 0.001). ROCs of 1-, 3- and 5-year survival revealed that the AUC values of the prognostic model were all > 0.7, with values of 0.779, 0.746, and 0.731, respectively. In addition, Gene Set Enrichment Analysis (GSEA) suggested that several tumor-related pathways were enriched in the high-risk group, while several immune­related pathways were enriched in the low-risk group. Patients in the low-risk group had higher immune scores and their immune cells and immune pathways were more active. Patients in the low-risk group had higher PD-1 and CTLA-4 levels and received more benefits from immune checkpoint inhibitors (ICIs) therapy. Discussion: The ARlncRNA prognostic model showed good performance in predicting the prognosis of patients with BRCA and is of great significance to guide the individualized treatment of these patients.

Molecular Mechanism of Secondary Endocrine Resistance in Luminal Breast Cancer.

OBJECTIVE: The molecular mechanism of secondary resistance in Luminal breast cancer was studied to provide new ideas for the treatment of breast cancer. METHODS: The sensitivity of the downregulation of myeloid leukemia factor 1-interacting proteins (MLF1IP) to Tamoxifen (TAM) was tested by the Cell Counting Kit-8 (CCK-8). The apoptosis of MLF1IP-mediated resistance was analyzed by flow cytometry (FCM) with/without TAM. Western blot was used in detecting various kinds of apoptosis and the expression of the protein related to the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway to study the molecular mechanism of secondary endocrine resistance in Luminal breast cancer. RESULTS: The downregulation of MLF1IP could significantly increase the drug sensitivity of Michigan Cancer Foundation-7 (MCF-7) cells and also inhibit the proliferation of MCF-7 cells under the stimulation of drugs. Western blot results showed that the expression of Bcl-2-associated X (BAX), Caspase3, Caspase7, and Caspase9 proteins increased when MLF1IP was downregulated. The results of the PI3K/AKT signaling pathway revealed that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression of MCF7-shRNA was higher than that of MCF7-NC cells, while the expression of p-AKT was lower than that of MCF7-NC cells. CONCLUSIONS: (1) MLF1IP-related apoptosis resistance plays an essential role in MLF1IP-mediated secondary resistance of breast cancer cells. (2) MLF1IP promotes AKT phosphorylation by inhibiting the PTEN expression, thus activating the PI3K/AKT signaling pathway and causing the secondary resistance of Luminal breast cancer. (3) MLF1IP can be used as a factor to predict the endocrine resistance of Luminal breast cancer.

SOX4 promotes the growth and metastasis of breast cancer.

PURPOSE: Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo. METHODS: We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging. RESULTS: SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel. CONCLUSIONS: SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

Sex differences in subclinical hypothyroidism and associations with metabolic risk factors: a health examination-based study in mainland China.

BACKGROUND: The association between subclinical hypothyroidism (SCH) and metabolic risk factors in the general health examination-based population has been widely explored. However, the results have been inconclusive. Additionally, the sex differences in the prevalence of SCH and the association of SCH with metabolic risk factors remain unknown. METHODS: We conducted this cross-sectional study using data from health examination-based participants between June 2016 and April 2018 in our health examination centre. Sex differences SCH and the association of SCH with metabolic risk factors were explored. RESULTS: The total prevalence of SCH was 3.40% among the 5319 included participants, and 4.90% among the 2306 female participants, which was much higher than the prevalence of 2.26% among the 3013 male participants (p < 0.05). In males, the difference between participants younger than 60 and aged 60 or older was not significant (p = 0.104); while in females, the difference between participants younger than 40 and participants aged 40 or older was statistically significant (p = 0.023). Multivariate logistic regression analysis demonstrated that age (OR = 0.568, p = 0.004), body-mass index (BMI) (OR = 5.029, p < 0.001) and systolic/diastolic blood pressure (SBP/DBP) (OR = 5.243, p < 0.001) were independent predictors of SCH in females, but no metabolic risk factor was significantly associated with SCH in males. Further analysis revealed that the prevalence was much higher in participants with one or two metabolic risk factors than in those with no above metabolic risk factors regardless of age (p < 0.01). CONCLUSIONS: Our study demonstrates that high BMI and/or high blood pressure are associated with SCH in female participants, and the prevalence of SCH among women with one or two metabolic risk factors ranges from 7.69-14.81%, which indicates that in such a population, serum concentrations of TSH and FT4 may be routinely screened in mainland China. Certainly, prospective, large-scale studies with long follow-up period are still necessary to further verify our results.

Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing.

BACKGROUND: Partner and localizer BRCA2 (PALB2) is a breast cancer predisposition gene, but the clinical relevance of PALB2 germline mutations in Chinese patients with breast cancer remains unknown. This study attempted to investigate the full prevalence and spectrum of PALB2 germline mutations in China and the associations between PALB2 germline mutations and breast cancer risk. METHODS: A total of 21,216 unselected patients with breast cancer were enrolled from 10 provinces in China, and 5890 Chinese women without cancer were enrolled as healthy controls. PALB2 screening was based on next-generation sequencing. RESULTS: A total of 16,501 BRCA1/2-negative patients with breast cancer were analyzed. Deleterious PALB2 mutation carriers accounted for 0.97% (n = 160) in the breast cancer cohort and for 0.19% (n = 11) in the healthy control cohort. Forty-one novel PALB2 germline mutations were identified. A high frequency of PALB2 c.751C>T was detected, and it accounted for 10.63% of the PALB2 germline mutations detected (17 of 160). PALB2 mutations were significantly associated with increased breast cancer risk (odds ratio [OR], 5.23; 95% confidence interval [CI], 2.84-9.65; P < .0001), especially among women 30 years old or younger (OR, 10.09; 95% CI, 3.95-25.79; P < .0001). Clinical characteristics, including a family history, bigger tumor size, triple-negative breast cancer, positive lymph nodes, and bilateral breast cancer, were closely related to PALB2 mutations. CONCLUSIONS: This study revealed a comprehensive spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer in China. PALB2 germline mutations confer a moderately increased risk for breast cancer but profoundly increase breast cancer risk for those 30 years old or younger in the Chinese population.

Male sex is associated with aggressive behaviour and poor prognosis in Chinese papillary thyroid carcinoma.

The differences in prognosis of papillary thyroid carcinoma (PTC) by sex have been investigated in several previous studies, but the results have not been consistent. In addition, the impact of sex on the clinical and pathological characteristics, especially on central lymph node metastasis (CLNM), still remains unknown. To the best of our knowledge, the impact of sex on PTC has not been investigated in the Chinese PTC population. Therefore, our study retrospectively analysed the data of 1339 patients who were diagnosed with PTC and had received radical surgery at Ningbo Medical Center, Lihuili Hospital. In addition to cancer-specific death, structural recurrence and risk stratification, prognosis was also estimated by using three conventional prognostic systems: AMES (age, distant metastasis, extent, size), MACIS (distant metastasis, age, completeness of resection, local invasion, size) and the 8th version TNM (tumor, lymph node, metastasis) staging system. The clinical and pathological characteristics and above prognostic indexes were compared between male and female PTC patients. The results showed that there were higher rates of non-microcarcinoma PTC (nM-PTC), CLNM, lateral lymph node metastasis (LLNM), advanced disease and bilateral disease, but there was a lower rate of concurrent Hashimoto's thyroiditis (HT) in male PTC patients than in female PTC patients. Additionally, the rate of intermediate-risk, high-risk or advanced disease was higher in male PTC patients. The above findings indicate that PTC in men is a more aggressive disease and may have a worse prognosis; thus, it should be treated with more caution.

Predictors for malignancy risk in subcentimeter thyroid nodules categorized as atypia/follicular lesion of undetermined significance by fine needle aspiration.

Little work has been done on the prediction of malignancy risk in patients with subcentimeter thyroid nodule (TN) categorized as atypia/follicular lesion of undetermined significance (AUS/FLUS). We performed a retrospective analysis on the medical records of subcentimeter TNs whose initial fine-needle aspiration (FNA) diagnosis was AUS/FLUS at our center between November 2013 and August 2018. Univariate analysis and multivariate logistic regression analysis were used to select independent factors associated with malignancy. Of the 324 patients who were classified as AUS/FLUS on initial FNA, 153 patients underwent surgical procedures and showed an associated malignancy rate of 45.10% (69/153). The malignancy rates in AUS/FLUS settings with and without repeat FNA were 38.30% (18/47), and 48.11% (51/106), respectively, p = 0.260. Multivariate logistic regression analysis revealed that age < 55 (OR 3.015, 95% CI 1.196-7.596), microcalcification (OR 9.162, 95% CI 3.332-25.916) and taller than wide shape (OR 10.785, 95% CI 4.108-28.319) were three independent predictors for malignancy. The malignancy rates in the patients with one or none of predictor and patients with two or three above predictors were 20.5% (17/83) and 74.3% (52/70), respectively, p < 0.001 (OR 11.216, 95% CI 5.266-23.885). In conclusion, our study showed that for subcentimeter TNs with AUS/FLUS category, patient's age, taller than wide shape and microcalcification were three independent predictive factors for malignancy, which was helpful for decision-making of surgery or observation in such patient population.

Long noncoding RNA ADPGK-AS1 promotes cell proliferation, migration, and EMT process through regulating miR-3196/OTX1 axis in breast cancer.

Emerging evidences exposed that long noncoding RNAs (lncRNAs) play important roles in various tumor progression including breast cancer (BC). However, the role of lncRNA ADP-dependent glucokinase antisense RNA 1 (ADPGK-AS1) in BC progression remains undiscovered. Hence, this study aimed to investigate the role of ADPGK-AS1 in BC. qRT-PCR was performed to investigate ADPGK-AS1 expression level in BC tissues and cell lines. The effect of ADPGK-AS1 knockdown on BC cellular process was assessed by loss-of-function assay. Luciferase reporter and RIP assay were performed to investigate the combination between ADPGK-AS1 and miR-3196. The combination between miR-3196 and orthodenticle homeobox 1 (OTX1) was verified by luciferase reporter assay. Finally, rescue assays were performed to confirm the effects of ADPGK-AS1/miR-3196/OTX1 axis on BC development. ADPGK-AS1 expression level was upregulated in BC tissues and cell lines. High expression of ADPGK-AS1 predicted poor prognosis for BC patients. Functionally, ADPGK-AS1 promoted cell proliferation, migration, induced epithelial-mesenchymal transition (EMT) process, and suppressed cell apoptosis. Mechanistically, ADPGK-AS1 acted as a miR-3196 sponge to release OTX1 in BC cells. Currently, ADPGK-AS1 acted as a competing endogenous RNA (ceRNA) via modulating miR-3196/OTX1 axis in BC.

Long non-coding RNA MIF-AS1 promotes breast cancer cell proliferation, migration and EMT process through regulating miR-1249-3p/HOXB8 axis.

Breast cancer (BC) is one of the leading cause of cancer-related death among females worldwide. Mounting evidences indicate that long non-coding RNAs (lncRNAs) were involved in tumor progression by acting as either oncogenes or tumor suppressors in multiple cancers. In this study, we focused on the function and mechanism of lncRNA Migration Inhibitory Factor Antisense RNA 1 (MIF-AS1) in BC. qRT-PCR showed that MIF-AS1 was upregulated in BC tissues and cells. To detect its bio-function, a series of loss-of-function assays were carried out. Thereafter, we found that MIF-AS1 depletion inhibited BC cell proliferation, migration and epithelial-mesenchymal transition (EMT). Recently, increasing studies indicate that lncRNAs can function as competing endogenous RNAs (ceRNAs). Using bioinformatics analysis and luciferase reporter assay, we identified that MIF-AS1 regulated the level of Homeobox B8 (HOXB8) via binding to miR-1249-3p. Taken all together, our findings proved that MIF-AS1 acted as a ceRNA by modulating miR-1249-3p/HOXB8 axis in breast cancer. LncRNA MIF-AS1 might be a new biomarker and therapeutic target for BC patients.

LINC01433/miR-2116-3p/MYC Feedback Loop Promotes Cell Proliferation, Migration, and the Epithelial-Mesenchymal Transition in Breast Cancer.

Background: It is reported that long noncoding RNAs play an important role in human cancers, including breast cancer (BC). However, the effect of long intergenic non-protein coding RNA 1433 (LINC01433) on BC development remains elusive. Materials and Methods: The expression level of LINC01433 in BC cells and a normal breast epithelial cell (MCF-10A) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). A series of functional assays was applied to measure the bio-function of LINC01433 in BC. Bioinformatics analysis and mechanistic assays were utilized to disclose the underlying mechanism involved in the LINC01433-mediated BC cellular process. Results: qRT-PCR revealed that LINC01433 was highly expressed in BC cells. In function, LINC01433 depletion suppressed BC cell proliferation, migration, and epithelial-mesenchymal transition, but induced cell apoptosis. Mechanically, chromatin immunoprecipitation and luciferase reporter assays suggested that LINC01433 was activated by its upstream transcription factor MYC proto-oncogene (MYC). The interaction between LINC01433 and miR-2116-3p was verified in BC. Additionally, MYC was validated as a target gene of miR-2116-3p. Rescue assays demonstrated that LINC01433 promoted BC cellular process via regulating miR-2116-3p/MYC axis. Conclusion: Our findings revealed a novel positive feedback loop (LINC01433/miR-2116-3p/MYC) in BC progression and discovered the novel functional genes in this BC cellular process.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules <10 mm in the maximum diameter: does size matter?

OBJECTIVE: Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) is a safe and effective method of screening malignant thyroid nodules such as papillary thyroid carcinoma. However, not much data are available regarding the diagnostic efficacy of US-FNAB for papillary thyroid microcarcinoma (≤10 mm in diameter). We aim to compare the diagnostic efficacy of US-FNAB on thyroid nodules between two groups divided by a diameter of 10 mm by correlating the cytological results of US-FNAB with the histopathologic diagnoses in selected patients. PATIENTS AND METHODS: Eight hundred twenty-two thyroid nodules (Group A: diameter ≤10 mm, n=620; Group B: diameter >10 mm, n=202) from 797 patients treated between March 2014 and June 2017 were retrospectively evaluated. Only nodules with Thyroid Imaging Reporting and Data System (TIRADS) categories 4-6 were enrolled and sampled by US-FNAB, followed by surgical resection. RESULTS: According to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories, 94 thyroid nodules were classified as I, III and IV, and were excluded from the analysis. The resultant 728 thyroid nodules from 721 patients were analyzed. The malignant tendency (TBSRTC V and VI) rates on US-FNAB were 88.2% and 84.6% (P=0.202) in Group A and Group B, respectively, and the malignant rates were 89.5% and 86.9% (P=0.330), respectively, on histopathology. There was a high concordance between cytology and histopathology diagnoses (kappa value =0.797), and no statistical difference in terms of US-FNAB accuracy was found between the two groups (P=0.533). CONCLUSION: For thyroid nodules of TIRADS category 4-6, the diagnostic efficacy of US-FNAB is similar for thyroid nodules either smaller or greater than 10 mm in their maximum diameter.