Breast metastasis from lung adenocarcinoma: a case report and review of the literature.

Lung cancer (LC) is one of the most lethal and most prevalent malignant tumors, and lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Breast cancer (BC) is the most common cancer worldwide, but metastases to the breast from extramammary neoplasms are rare, especially from the lung. Early diagnosis and differentiation of primary from metastatic breast carcinoma are essential. Here, we present a case of metastases to the breast from lung adenocarcinoma, the treatment options varied according to disease progression.

The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells.

Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used for in vitro and in vivo experiments, respectively. Western blot analysis is used to detect the protein expressions of DUBs, zinc finger E-box binding homeobox 1 (ZEB1), and epithelial-mesenchymal transition (EMT)-related markers. Colony formation and transwell assays are used to detect the proliferation, migration and invasion of TNBC cells. Wound healing assay is used to detect the mobility of TNBC cells. Immunoprecipitation assay is used to detect the interaction between breast cancer susceptibility gene 1/2-containing complex subunit 3 (BRCC3) and ZEB1. ZEB1 ubiquitination levels, protein stability, and protein degradation are also examined. Pathological changes in the lung tissues are detected via HE staining. Our results show a significant positive correlation between the expressions of BRCC3 and ZEB1 in clinical TNBC tissues. Interference with BRCC3 inhibits TNBC cell proliferation, migration, invasion and EMT. BRCC3 interacts with ZEB1 and interferes with BRCC3 to inhibit ZEB1 expression by increasing ZEB1 ubiquitination. Interference with BRCC3 inhibits TNBC cell tumorigenesis and lung metastasis in vivo. In all, this study demonstrates that BRCC3 can increase the stability of ZEB1, upregulate ZEB1 expression, and promote the proliferation, migration, invasion, EMT, and metastasis of TNBC cells, providing a new direction for cancer therapy.

Vasculogenic mimicry regulates immune infiltration and mutational status of the tumor microenvironment in breast cancer to influence tumor prognosis.

BACKGROUND: Vasculogenic mimicry (VM) refers to the direct formation of microcirculatory ducts by invasive malignant tumors via cellular phenotypic transformation. However, there is a lack of VM-based biomarkers for breast cancer. METHODS: We obtained transcriptomic expression data, single cell sequencing data, and clinical data of patients from The Cancer Genome Atlas Program (TCGA) database and GEO database, performed single cell analysis to obtain specific type annotations of breast cancer cells and analyzed their spatial expression analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses as well as Gene Set Enrichment Analysis (GSEA) analyses were performed to clarify the biological pathways and tumor functional enrichment relationships of the major expressed genes of VM in the breast cancer bulk data specimens. VM biomarkers were constructed. Meanwhile, the relationship between VM scores and tumor immune infiltration in breast cancer was analyzed using MCPcounter and ssGSEA methods. In addition, we assessed the specific relationship between NDRG1, a key VM gene in breast cancer, and tumor colonization, adhesion and invasion by biological experiments in breast cancer cell lines. RESULTS: The main cell types of breast cancer (BRCA) samples were annotated by single cell transcriptome analysis. Most of the VM-high group was present in epithelial cells, whereas the VM-low group was present in immune and stromal cells. Multiple tumor pathways such as TGFß p53 and MAPK were closely associated with VM-mediated breast cancer infiltration and invasion. A prognostic model of breast cancer based on VM key genes was constituted. Prognostic stratification of breast cancer was successfully achieved for the TCGA-BRCA and GSE58812 datasets. Through immune infiltration analysis, we found that differential expression of VM markers was associated with multiple immune cell regulation. In MDA-MB-231 and MDA-MB-453 cell lines, we found that the NDRG1 gene significantly promoted colony formation of breast cancer cells. CONCLUSION: Our constructed VM-related gene-based model of breast cancer biology holds promise for prognostic prediction and patient stratification of breast cancer. This may provide a potentially clinically valuable aid in promoting a deeper understanding of the biological regulation of VM in breast cancer and exploring the specific mechanisms of tumor angiogenesis and breast cancer development.

Real-world outcomes for Chinese breast cancer patients with tumor location of central and nipple portion.

Background: The association between tumor location and breast cancer prognosis has been controversial. We sought to explore the relationship between tumors located in central and nipple portion (TCNP) and Chinese breast cancer. Patients and methods: A total of 1,427 breast cancer patients were recruited. There were 328 cases of TCNP and 1,099 cases of tumors in the breast peripheral quadrant (TBPQ). The chi-square test was used to compare different variables between TCNP and TBPQ groups. A one-to-one propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of TCNP and TBPQ groups. Kaplan-Meier curves were used for survival analysis of disease-free survival (DFS), breast cancer-specific survival (BCSS) and overall survival (OS). The Cox proportional hazards regression model was applied to identify prognostic risk factors. Results: The median follow-up time was 58 months. Compared to TBPQ, TCNP patients had significantly larger tumor size, more frequent metastasis to lymph nodes (LN) and more proportions of TNM stage II-III. DFS, OS and BCSS rates were markedly lower in the TCNP group as compared to the TBPQ group before and after PSM (all p < 0.05). Multivariate Cox analysis showed that TCNP was an independent prognostic factor for breast cancer. Subgroup analysis indicated that for breast molecular subtypes and TNM stage II-III breast cancer, TCNP were related to worse prognosis. Multivariate logistic regression revealed that TCNP was an independent contributing factor for LN metastasis. Conclusion: In Chinese breast cancer, compared to TBPQ, TCNP is associated with more LN metastasis and poorer prognosis.

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.

Male Breast Carcinoma Metastatic to the Choroid: A Case Report and Opinions of Management.

Male breast carcinoma metastatic to the choroid is very rare and often related to poor prognosis. Herein, we report the findings in a Chinese male breast cancer patient who developed choroidal metastasis, and give opinions on systemic treatments. A 45-year-old Chinese male represented with difficulty breathing and visual impairment in the left eye 6 years after his breast cancer surgery and postoperative adjuvant treatment. PET/CT revealed multi-organs metastasis of the patient. The IHC indicated the lung lesion to be originated from the breast (ER+/PR+/HER2-). Eye examination provided evidence for breast cancer choroidal metastasis. Two cycles of TX (docetaxel + capecitabine) followed by two courses of GP (gemcitabine + cis-platinum) were applied as salvage chemotherapy. Metastases in his lung and bone remained stable. As for choroidal metastasis, a regimen of CDK4/6 inhibitor (Palbociclib) plus fulvestrant was recommended to the patient, which led to a good response. Notably, CDK4/6 inhibitor combined with endocrine therapy may be considered as an effective treatment for hormonal receptor-positive breast cancer patients with choroidal metastasis. We recommend that eye examination should not be neglected in breast cancer patients.

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

Development and Validation of a Nomogram for Preoperative Prediction of Central Compartment Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma and Type 2 Diabetes Mellitus.

PURPOSE: To develop and validate a nomogram to predict central compartment lymph node metastasis in PTC patients with Type 2 Diabetes. PATIENTS AND METHODS: The total number of enrolled patients was 456. The optimal cut-off values of continuous variables were obtained by ROC curve analysis. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated and presented in a nomogram. The ROC curve analysis was performed to evaluate the discrimination of the nomogram, calibration curves and Hosmer-Lemeshow test were used to visualize and quantify the consistency. Decision curve analysis (DCA) was performed to evaluate the net clinical benefit patients could get by applying this nomogram. RESULTS: ROC curve analysis showed the optimal cutoff values of NLR, PLR, and tumor size were 2.9204, 154.7003, and 0.95 (cm), respectively. Multivariate logistic regression analysis indicated that age, multifocality, largest tumor size, and neutrophil-to-lymphocyte ratio were independent prognostic factors of CLNM. The C-index of this nomogram in the training data set was 0.728, and 0.618 in the external validation data set. When we defined the predicted possibility (>0.5273) as high-risk of CLNM, we could get a sensitivity of 0.535, a specificity of 0.797, a PPV(%) of 67.7, and an NPV(%) of 68.7. Great consistencies were represented in the calibration curves. DCA showed that applying this nomogram will help patients get more clinical net benefit than having all of the patients or none of the patients treated with central compartment lymph node dissection (CLND). CONCLUSION: A high level of preoperative NLR was an independent predictor for CLNM in PTC patients with T2DM. And the verified optimal cutoff value of NLR in this study was 2.9204. Applying this nomogram will help stratify high-risk CLNM patients, consequently enabling these patients to be treated with appropriate measures. What is more, we hope to find more sensitive indicators in the near future to further improve the sensitivity and specificity of our nomogram.

Transcutaneous electroacupuncture alleviates postoperative ileus after gastrectomy: A randomized clinical trial.

AIM: To investigate the efficacy and safety of transcutaneous electroacupuncture (TEA) to alleviate postoperative ileus (POI) after gastrectomy. METHODS: From April 2014 to February 2017, 63 gastric cancer patients were recruited from the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. After gastrectomy, the patients were randomly allocated to the TEA (n = 33) or control (n = 30) group. The patients in the TEA group received 1 h TEA on Neiguan (ST36) and Zusanli (PC6) twice daily in the morning and afternoon until they passed flatus. The main outcomes were hours to the first flatus or bowel movement, time to nasogastric tube removal, time to liquid and semi-liquid diet, and hospital stay. The secondary outcomes included postoperative symptom assessment and complications. RESULTS: Time to first flatus in the TEA group was significantly shorter than in the control group (73.19 ± 15.61 vs 82.82 ± 20.25 h, P = 0.038), especially for open gastrectomy (76.53 ± 14.29 vs 87.23 ± 20.75 h, P = 0.048). Bowel sounds on day 2 in the TEA group were significantly greater than in the control group (2.30 ± 2.61/min vs 1.05 ± 1.26/min, P = 0.017). Time to nasogastric tube removal in the TEA group was earlier than in the control group (4.22 ± 1.01 vs 4.97 ± 1.67 d, P = 0.049), as well as the time to liquid diet (5.0 ± 1.34 vs 5.83 ± 2.10 d, P = 0.039). Hospital stay in the TEA group was significantly shorter than in the control group (8.06 ± 1.75 vs 9.40 ± 3.09 d, P = 0.041). No significant differences in postoperative symptom assessment and complications were found between the groups. There was no severe adverse event related to TEA. CONCLUSION: TEA accelerated bowel movements and alleviated POI after open gastrectomy and shortened hospital stay.