An unsupervised learning model based on CT radiomics features accurately predicts axillary lymph node metastasis in breast cancer patients-diagnostic study.

BACKGROUND: The accuracy of traditional clinical methods for assessing the metastatic status of axillary lymph nodes is unsatisfactory. In this study, we propose the use of radiomic technology and three-dimensional (3D) visualization technology to develop an unsupervised learning model for predicting axillary lymph node metastasis in patients with breast cancer, aiming to provide a new method for clinical axillary lymph node assessment in patients with this disease. METHODS: In this study, we retrospectively analyzed the data of 350 patients with invasive breast cancer who underwent lung-enhanced CT and axillary lymph node dissection (ALND) surgery at the Department of Breast Surgery of the XXX Hospital of XXX University. We used 3D visualization technology to create a 3D atlas of axillary lymph nodes and identified the region of interest (ROI) for the lymph nodes. Radiomic features were subsequently extracted and selected, and a prediction model for axillary lymph nodes was constructed using the K-means unsupervised algorithm. To validate the model, we prospectively collected data from 128 breast cancer patients who were clinically evaluated as negative at our center. RESULTS: Using 3D visualization technology, we extracted and selected a total of 36 CT radiomics features. The unsupervised learning model categorized 1737 unlabeled lymph nodes into two groups, and the analysis of the radiomic features between these groups indicated potential differences in lymph node status. Further validation with 1397 labeled lymph nodes demonstrated that the model had good predictive ability for axillary lymph node status, with an area under the curve (AUC) of 0.847 (0.825-0.869). Additionally, the model's excellent predictive performance was confirmed in the 128 axillary clinical assessment negative cohort (cN0) and the 350 clinical assessment positive (cN+) cohort, for which the correct classification rates (CCR) were 86.72% and 87.43%, respectively, which were significantly greater than those of clinical assessment methods. CONCLUSIONS: We created an unsupervised learning model that accurately predicts the status of axillary lymph nodes. This approach offers a novel solution for the precise assessment of axillary lymph nodes in patients with breast cancer.

Comparison of neoadjuvant chemotherapy response and prognosis between HR-low/HER2-negative BC and TNBC: an exploratory real-world multicentre cohort study.

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.

Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.

METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2-breast cancer.

BACKGROUND: Chemotherapy is an important strategy for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+HER2-) breast cancer (BC), but this subtype has a low response rate to chemotherapy. Growing evidence indicates that N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells and that methyltransferase-like 3 (METTL3) participates in tumour progression in several cancer types. Therefore, exploring the function of METTL3 in HR+HER2- BC initiation and development is still important. METHODS: mRNA and protein expression levels were analysed by quantitative real-time polymerase chain reaction and western blotting, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. Cell cycle progression was assessed by flow cytometry. Cell migration and invasion were analysed by wound healing assays and transwell assays, respectively, and apoptosis was analysed by TUNEL assays. Finally, m6A modification was analysed by methylated RNA immunoprecipitation. RESULTS: Chemotherapy-induced downregulation of the m6A modification is regulated by METTL3 depletion in HR+HER2- BC. METTL3 knockdown in MCF-7/T47D cells decreased the drug sensitivity of HR+HER2- BC cells by promoting tumour proliferation and migration and inhibiting apoptosis. Mechanistically, CDKN1A is a downstream target of METTL3 that activates the AKT pathway and promotes epithelial-mesenchymal transformation (EMT). Moreover, a decrease in BAX expression was observed when m6A modification was inhibited with METTL3 knockdown, and apoptosis was inhibited by the reduction of caspase-3/-9/-8. CONCLUSION: METTL3 depletion promotes the proliferation and migration and decreases the drug sensitivity of HR+HER2- BC via regulation of the CDKN1A/EMT and m6A-BAX/caspase-9/-3/-8 signalling pathways, which suggests METTL3 played a tumour-suppressor role and it could be a potential biomarker for predicting the prognosis of patients with HR+HER2- BC.

RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

3D reconstruction based novel methods are more effective than traditional clinical assessment in breast cancer axillary lymph node metastasis prediction.

The status of axillary lymph node metastases determines the treatment and overall survival of breast cancer (BC) patients. Three-dimensional (3D) assessment methods have advantages for spatial localization and are more responsive to morphological changes in lymph nodes than two-dimensional (2D) assessment methods, and we speculate that methods developed using 3D reconstruction systems have high diagnostic efficacy. This exploratory study included 43 patients with histologically confirmed BC diagnosed at Second Xiangya Hospital of Central South University between July 2017 and August 2020, all of whom underwent preoperative CT scans. Patients were divided into a training cohort to train the model and a validation cohort to validate the model. A 3D axillary lymph node atlas was constructed on a 3D reconstruction system to create various methods of assessing lymph node metastases for a comparison of diagnostic efficacy. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of these methods. A total of 43 patients (mean [SD] age, 47 [10] years) met the eligibility criteria and completed 3D reconstruction. An axillary lymph node atlas was established, and a correlation between lymph node sphericity and lymph node metastasis was revealed. By continuously fitting the size and characteristics of axillary lymph nodes on the 3D reconstruction system, formulas and models were established to determine the presence or absence of lymph node metastasis, and the 3D method had better sensitivity for axillary lymph node assessment than the 2D method, with a statistically significant difference in the correct classification rate. The combined diagnostic method was superior to a single diagnostic method, with a 92.3% correct classification rate for the 3D method combined with ultrasound. In addition, in patients who received neoadjuvant chemotherapy (NAC), the correct classification rate of the 3D method (72.7%) was significantly higher than that of ultrasound (45.5%) and CT (54.5%). By establishing an axillary lymph node atlas, the sphericity formula and model developed with the 3D reconstruction system achieve a high correct classification rate when combined with ultrasound or CT and can also be applied to patients receiving NAC.

Prognostic value of tumor mutation burden and the relationship between tumor mutation burden and immune infiltration in HER2+ breast cancer: a gene expression-based study.

BACKGROUND: Whether tumor mutation burden (TMB) correlated with improved survival outcomes or promotion of immunotherapies remained controversy in various malignancies. We aimed to explore the prognostic value of TMB and the relationship between TMB and immune infiltration in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: We downloaded somatic mutation data and clinical information for 216 HER2+ BC patients from the The Cancer Genome Atlas (TCGA) and cBioPortal databases. Patients were divided into high- and low-TMB groups through TMB calculation. Cox regression analysis was used to establish an immune- and mutant-related risk model based on 5-hub genes. The relationship between 5-hub genes mutants and the level of immune infiltration, as well as the relationship between the risk model and the immune microenvironment were analyzed by "TIMER" database. RESULTS: TMB was negatively correlated with overall survival (OS) and disease-free survival (DFS), and high TMB may inhibit immune infiltration in HER2+ BC. Furthermore, risk score classified effectively patients into low- and high-risk groups in training and validation cohorts. The infiltration of CD4+ T cells and NK cells and the levels of immune checkpoint pathway genes were lower in the high-risk group, which indicated a poor prognosis. CONCLUSIONS: Higher TMB correlated with poor survival outcomes and might inhibit the immune infiltrates in HER2+ BC. The 5-hub TMB-related signature conferred lower immune cells infiltration which deserved further validation.

Construction and validation of a risk prediction model for clinical axillary lymph node metastasis in T1-2 breast cancer.

The current diagnostic technologies for assessing the axillary lymph node metastasis (ALNM) status accurately in breast cancer (BC) remain unsatisfactory. Here, we developed a diagnostic model for evaluating the ALNM status using a combination of mRNAs and the T stage of the primary tumor as a novel biomarker. We collected relevant information on T1-2 BC from public databases. An ALNM prediction model was developed by logistic regression based on the screened signatures and then internally and externally validated. Calibration curves and the area under the curve (AUC) were employed as performance metrics. The prognostic value and tumor immune infiltration of the model were also determined. An optimal diagnostic model was created using a combination of 11 mRNAs and T stage of the primary tumor and showed high discrimination, with AUCs of 0.828 and 0.746 in the training sets. AUCs of 0.671 and 0.783 were achieved in the internal validation cohorts. The mean external AUC value was 0.686 and ranged between 0.644 and 0.742. Moreover, the new model has good specificity in T1 and hormone receptor-negative/human epidermal growth factor receptor 2- negative (HR-/HER2-) BC and good sensitivity in T2 BC. In addition, the risk of ALNM and 11 mRNAs were correlated with the infiltration of M2 macrophages, as well as the prognosis of BC. This novel prediction model is a useful tool to identify the risk of ALNM in T1-2 BC patients, particularly given that it can be used to adjust surgical options in the future.

Chemotherapy significantly improves long-term survival of small lesion node negative metaplastic breast carcinoma in T1c population rather than T1a and T1b.

Metaplastic breast carcinoma (MpBC) is considered a highly aggressive disease, the outcome of chemotherapy on small lesions (T1abcN0M0) MpBC patients remain unclear. We identified 890 female MpBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. After propensity score matching (PSM), 584 patients were matched. Survival probability was compared among T1a, T1b, and T1c patients and between patients with and without chemotherapy using Kaplan-Meier analysis and Cox proportional hazard analysis. Significance was set at two-sided P < 0.05. We classified 49, 166, and 675 patients as T1a, T1b, and T1c MpBC, respectively. The chemotherapy group included 404 patients (45.4%). Following PSM, survival analysis indicated that the patients who underwent chemotherapy had higher OS (P = 0.0002) and BCSS (P = 0.0276) in the T1c substage, but no significant difference was detected in T1a or T1b patients. In this population-based study, small lesion MpBC showed a favorable prognosis. Chemotherapy improved the prognosis of T1c MpBC patients but not T1a and T1b patients to a beneficial extent. Our findings may offer novel insight into a therapeutic strategy for MpBC.

Prognosis Comparison Between Nipple-Sparing Mastectomy and Total Mastectomy in Breast Cancer: A Case-Control Study After Propensity Score Matching.

BACKGROUND: Currently, the operation rate of nipple-sparing mastectomy (NSM) is increasing. However, the long-term prognosis of NSM is not well documented. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term prognosis of NSM compared with total mastectomy (TM). METHODS: Population-level data of female breast cancer patients treated with NSM and TM were extracted from 1998 to 2016 from the SEER database. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables in comparisons. Kaplan-Meier analysis, log-rank test, and Cox proportional hazard regression were performed. RESULTS: A total of 5765 patients underwent NSM, which increased from 266 in 2004-2009 to 5370 in 2010-2016. A total of 134,528 patients underwent TM, and the number of patients undergoing TM continued to decline. The overall survival (OS) and breast cancer-specific survival (BCSS) were similar between the NSM group and the TM group (P = 0.058 and 0.87, respectively). For OS, subgroup analysis showed that patients with age ≥ 46, White race, median household income ≥ $70,000, hormone receptor-positive, and HER2 negative had a better prognosis for treatment with NSM. There was no significant difference in BCSS between the NSM group and the TM group. CONCLUSIONS: In recent years, the clinical application of NSM has been increasing. NSM is a proper procedure for breast cancer patients to achieve long-term survival.

A literature review of the promising future of TROP2: a potential drug therapy target.

Background and Objective: Previous studies have demonstrated that the oncogene trophoblast cell surface antigen 2 (TROP2) has great application prospects as a therapeutic target. However, few literature reviews have systematically summarized and evaluated its role in cancer therapy. This study aims to summarize the molecular structure, functions, signal transduction pathways, and prognostic value of TROP2, and explore therapeutic agents that target TROP2. Methods: A total of 1,376 published literatures from PubMed and 614 published literatures from EMBASE were retrieved by searching "TROP2" or "Trophoblast cell surface antigen 2". The search was conducted on December 12, 2020, and updated on November 20, 2022. The cBioportal and GEPIA (Gene Expression Profiling Interactive Analysis) databases were used to analyze the expression, mutation, and prognostic value of TROP2 in different types of cancer. Key Content and Findings: TROP2 is overexpressed in different tumor tissues and plays roles in cell proliferation, invasion, migration, apoptosis, and treatment resistance by binding to or interacting with several molecules. As a therapeutic target, TROP2 is particularly suitable for antibody-based therapies. Monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), virus-like particles, and antibody drugs in combination with traditional chemotherapy, immunotherapy, radioimmunotherapy, photoimmunotherapy, and nanoparticles that target TROP2 have thus far been rapidly developed. For example, sacituzumab govitecan (IMMU-132), a TROP2-targeting ADC, was granted accelerated approval for the treatment of metastatic triple-negative breast cancer (TNBC). Anti-TROP2 antibody-conjugated nanoparticles (ST-NPs) are a promising vehicle for delivering doxorubicin in targeted TNBC therapy. Conclusions: The availability of TROP2-targeting ADCs makes TROP2 an accessible and promising therapeutic target for advanced metastatic cancers. The present review describes the important role of TROP2 in tumorigenesis and its potential applications as a promising biomarker and therapeutic target that is capable of reversing resistance.

Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers.

BACKGROUND: The cumulative risk of distant recurrence of hormone receptor-positive (HR+) breast cancer in the past 20 years has ranged from 22% to 52% after 5 years of endo-therapy. The TNM stage, histological grade, and age are important clinical factors related to recurrence, however the exact mechanism of tamoxifen resistance is still unclear. METHODS: Differentially expressed genes (DEGs) were identified in 10 pairs of patients who had relapsed and non-relapsed after tamoxifen treatment based on matching their clinicopathological factors. After analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 10 hub genes were identified using Cytoscape software. Next, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used to verify the expression and overall survival (OS) of the 10 hub genes respectively, and GSE96058 and Kaplan-Meier Plotter website were used to further verify the OS of C3, CX3CL1, CXCL2, and SAA1. Finally, Immune Cell Abundance Identifier (ImmuCellAI) and the TIMER database were used to estimate immune cell infiltration and the expression of prognostic genes. RESULTS: The DEGs were mainly enriched in the inflammatory response and cytokine-receptor interaction. The expression and the survival analysis identified CX3CL1, CXCL2, and SAA1 as prognostic factors, whose overexpression in HR+/human epidermal growth factor receptor 2 (HER-2) negative breast cancer possibly predicted a longer disease-free survival. The expression levels of these 3 genes are positively correlated with immune cell infiltration. Their high expression levels may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be biomarkers for tamoxifen-resistant therapy. CONCLUSIONS: In conclusion, the high expression of CX3CL1, CXCL2, and SAA1 may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells.

[This retracts the article DOI: 10.3892/etm.2017.4593.].

Inhibition of autophagy with Chloroquine enhanced apoptosis induced by 5-aminolevulinic acid-photodynamic therapy in secondary hyperparathyroidism primary cells and organoids.

Secondary hyperparathyroidism (SHPT), the most common complication in the later stage of chronic kidney disease (CKD), seriously affects quality of life and the survival time of patients. At present, the conventional drugs and surgical methods still cannot fully meet the needs of clinical treatment. It is quite significant to develop effective and minimally invasive treatment methods. 5-Aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT), an alternative treatment relying on light irradiation, photosensitizer, and oxygen to produce a series of cytotoxic effects on tissue, is a promising technique for treating SHPT. We have successfully cultivated SHPT primary cells and organoids, and further proved that the amount of 5-ALA transformed into protoporphyrin IX in a time- and concentration-dependent manner. Also, 5-ALA-PDT exerted a cytotoxic effect on both primary cells and organoids by the cell counting kit (CCK-8) assay. Mechanically, 5-ALA-PDT increased the number of autophagosomes, and autophagy- and apoptosis-related proteins were upregulated markedly by western-blotting. The autophagy inhibitor Chloroquine (CQ) significantly increased the proportion of apoptotic cells, while the autophagy inducer rapamycin decreased the inhibitory ability of 5-ALA-PDT in SHPT primary cells. In brief, 5-ALA-PDT exhibits a phototoxic effect on SHPT primary cells and organoids. Autophagy and apoptosis are involved in the mechanism, and autophagy plays a role in promoting survival and inhibiting apoptosis. Therefore, the use of autophagy inhibitors can increase the sensitivity of SHPT cells and organoids treated with 5-ALA-PDT.

Surgery of the Primary Tumor Offers Survival Benefits of Breast Cancer with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis.

BACKGROUND: Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. METHODS: This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. RESULTS: A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. CONCLUSION: For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

Application of a Three-Dimensional Reconstruction System in Breast Cancer with Ipsilateral Supraclavicular Lymph Node Metastasis: A Case Series.

BACKGROUND: The role of supraclavicular lymph node dissection (SCLND) in breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLM) remains controversial. So far, there have been no effective imaging methods to precisely judge the feasibility of SCLND and the modes of ISLM. CASE REPORT: We innovatively applied a three-dimensional (3D) reconstruction system to assess the feasibility of SCLND preoperatively for 13 breast cancer patients with ISLM. Based on the 3D reconstruction system and intraoperative findings, we performed lymph node dissection of their lesion areas. Compared to computed tomography or ultrasonography, the 3D reconstruction system found more lymph nodes not only in the ipsilateral supraclavicular area but also in other areas in which metastasis may occur (p < 0.05), and provided visual images pertaining to the relationship between the lymph nodes and major blood vessels, nerves, and muscles. CONCLUSION: The 3D reconstruction system could significantly benefit the precise assessment of the lesion area and facilitate subsequent relevant surgery.

The Expression, Functions, Interactions and Prognostic Values of PTPRZ1: A Review and Bioinformatic Analysis.

Available studies demonstrate that receptor-type tyrosine-protein phosphatase zeta (PTPRZ1) is expressed in different tumor tissues, and functions in cell proliferation, cell adhesion and migration, epithelial-to-mesenchymal transition, cancer stem cells and treatment resistance by interacting with or binding to several molecules. These included pleiotrophin (PTN), midkine, interleukin-34, ß-catenin, VEGF, NF-κB, HIF-2, PSD-95, MAGI-3, contactin and ErbB4. PTPRZ1 was involved in survival signaling and could predict the prognosis of several tumors. This review discusses: the current knowledge about PTPRZ1, its expression, co-receptors, ligands, functions, signaling pathway, prognostic values and therapeutic agents that target PTPRZ1.

Long non-coding RNA PCAT6 targets miR-204 to modulate the chemoresistance of colorectal cancer cells to 5-fluorouracil-based treatment through HMGA2 signaling.

Colorectal cancer (CRC) is still the third most common cancer in the world with a limited prognosis due to the chemoresistance of CRC cells to 5-fluorouracil (5-FU)-based chemotherapy. In our previous study, we revealed that miR-204 overexpression could sensitize CRC cell to 5-FU treatment through targeting HMGA2/PI3K signaling pathway; however, miR-204 expression in CRC tissues is abnormally downregulated. Long non-coding RNAs (lncRNAs) dysregulation has been reported in human diseases, including cancer. Also, lncRNA can regulate cancer cell proliferation, invasion, migration, as well as chemoresistance. LncRNA prostate cancer-associated transcript 6 (PCAT6) acts as an oncogene in many cancers; herein, PCAT6 expression was abnormally upregulated in CRC tissues and cell lines, suggesting its potential role in CRC. Further, we assessed the specific function and mechanism of PCAT6 in CRC. Furthermore, we revealed that PCAT6 knockdown attenuated CRC chemoresistance to 5-FU through miR-204/HMGA2/PI3K; miR-204 inhibition could partially reverse the effect of PCAT6 knockdown. Taken together, we demonstrate that the abnormal PCAT6 overexpression inhibits miR-204 expression in CRC, thereby promoting HMGA2/PI3K signaling activity, ultimately enhancing the chemoresistance of CRC cells to 5-FU; PCAT6 represents a promising target for dealing with CRC chemoresistance.

Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells.

BACKGROUND: Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear. METHODS: We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA. RESULTS: We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway. CONCLUSIONS: Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

A TP73-AS1/miR-200a/ZEB1 regulating loop promotes breast cancer cell invasion and migration.

Breast cancer (BC) is one of the leading causes of cancer deaths worldwide and the most common cancer among women. In our previous study, we revealed that lncRNA TP73-AS1 promotes breast cancer cell proliferation through directly binding to miR-200a. Herein, we evaluated the effect of TP73-AS1 in breast cancer cell invasion and migration, and further demonstrated the direct binding between TP73-AS1 and miR-200a, between miR-200a and 3'UTR of ZEB1, an essential metastasis-related transcription factor. TP73-AS1 promoted ZEB1 expression via competing with ZEB1 3'UTR for miR-200a binding. Moreover, ZEB1 could bind to the promoter region of TP73-AS1 to activate its expression. TP73-AS1 and ZEB1 expression was up-regulated, whereas miR-200a expression was down-regulated in breast cancer tissues. Taken together, we demonstrated a TP73-AS1/miR-200a/ZEB1 regulating loop in breast cancer cells, which promote cancer cell invasion and migration through regulating E-cadherin and Twist expression. Suppressing TP73-AS1 expression to rescue miR-200a expression, thus to inhibit ZEB1 and Twist expression and up-regulate E-cadherin might improve breast cancer cell invasion and migration.