Clinical significance of low expression of CADM3 in breast cancer and preliminary exploration of related mechanisms.

BACKGROUND: Cell adhesion molecule 3 (CADM3), a transmembrane glycoprotein on cell membranes, plays a role in the way of ligand and receptor interaction. However, there are few studies on CADM3 in tumors, and how it works in breast cancer (BC) remains unclear. METHODS: The Cancer Genome Atlas (TCGA) database and clinical samples were used to analyze CADM3 expression and its correlation with clinicopathological factors and prognosis. Its correlation with immune infiltration was analyzed by TCGA. The effects of CADM3 on proliferation and migration were investigated by cell clonal formation, CCK-8, cell scratch and transwell assay. Protein interaction network was prepared and the function prediction of related genes was conducted. The correlation between CADM3 and MAPK pathway was further explored by western blot experiment. RESULTS: The expression of CADM3 in BC tissues were significantly lower than that in adjacent normal tissues. High level of CADM3 was related to better prognosis of BC patients. CADM3 was an independent prognostic factor for BC. Expression of CADM3 was significantly associated with the status of ER and PR, age and PAM50 subtypes. CADM3 positively related to many immune infiltrating cells. Overexpression of CADM3 can notably reduce cell proliferation and migration. CADM3 was related to MAPK pathway and the phosphorylation of ERK1/2 and JNK1 was inhibited in BC cells with high CADM3. CONCLUSIONS: Our research reveals the clinical significance of CADM3 in BC and indicates the critical roles of CADM3 in immune infiltration and MAPK pathway.

High expression of CCDC69 is correlated with immunotherapy response and protective effects on breast cancer.

BACKGROUND: As a molecule controlling the assembly of central spindles and recruitment of midzone component, coiled-coil domain-containing protein 69 (CCDC69) plays an important role in multiple cancers. Currently, the relationships between CCDC69 and immune infiltration or immunotherapy in breast cancer remain unclear. METHODS: The expression and prognostic significance of CCDC69 in breast cancer were comprehensively analyzed by quantitative real-time PCR, immunohistochemical staining and various databases. The data source of differentially expressed genes, gene set enrichment analysis, and immune cell infiltration analysis came from The Cancer Genome Atlas (TCGA) database. Single-cell analysis based on IMMUcan database was used. The protein-protein interaction network was developed applying STRING, Cytoscape, CytoHubba, and GeneMANIA. TISIDB was employed in analyzing the CCDC69 co-expressed immune related genes. The correlations between CCDC69 and immunotherapy or immune-related scores were analyzed by CAMOIP and TISMO. Ctr-db was also used to conduct drug sensitivity analysis. RESULTS: The mRNA of CCDC69 was downregulated in breast cancer tissues compared with normal tissues. Higher CCDC69 expression was associated with a better breast cancer prognosis. Enrichment analysis showed that the co-expression genes of CCDC69 were mainly related to immune-related pathways. The expression of CCDC69 was found to be positively correlated with multiple tumor-suppression immune infiltration cells, especially T cells and dendritic cells. Meanwhile, high CCDC69 expression can predict better immunotherapy responses when compared with low CCDC69 expression. After the interferon-gamma treatment, the CCDC69 expression was elevated in vitro. CCDC69 expression was a reliable predictor for the response status of two therapeutic strategies in breast cancer. CONCLUSIONS: Our research revealed the clinical significance of CCDC69 in breast cancer and validated the critical roles of CCDC69 in the tumor immune infiltration and immunotherapy responses.

Multiple Metastases of the Liver and Lung After Breast-Conserving Surgery for Ductal Carcinoma In Situ Without Microinvasion of the Breast: A Case Report and Literature Review.

Background: Ductal carcinoma in situ (DCIS) is a non-invasive disease that rarely causes distant metastasis. It is extremely rare for patients diagnosed with DCIS without microinvasion to develop distant metastasis in the absence of ipsilateral or contralateral breast recurrence. This is the first case report of multiple liver and lung metastases from DCIS after breast-conserving surgery and radiotherapy. Case Presentation: A 45-year-old woman who was diagnosed with DCIS and received breast-conserving surgery, radiotherapy, and sequential endocrine therapy developed multiple metastases in the liver and lung despite not having bilateral breast recurrence at the 62-month follow-up. Comprehensive advanced breast cancer therapy was administered but did not prevent the progression of metastatic foci in the liver. Conclusions: This case shows the poor potential outcome in DCIS. Further research should be conducted on metastasis in DCIS; reexamination and monitoring are indispensable for patients diagnosed with DCIS.