GK921, a transglutaminase inhibitor, strengthens the antitumor effect of cisplatin on pancreatic cancer cells by inhibiting epithelial-to-mesenchymal transition.

Pancreatic adenocarcinoma (PAAD), a common digestive malignant tumor, presents high mortality rates and limited treatment methods. Currently, chemotherapy remains the main therapy method for patients with PAAD. As a classical chemotherapy drug, cisplatin (DDP) is limited by dose-related toxicity in patients with PAAD. In this study, we demonstrated that TGM2 may be a treatment and prognosis marker in pancreatic cancer patients. Co-treatment of low dose of DDP and GK921, a transglutaminase (TGM2) inhibitor, is capable of synergistically inhibiting the PAAD cell viability and proliferation in vitro and in vivo. Based on in vitro study, GK921 inhibited the epithelial-to-mesenchymal transition (EMT) induced by TGM2 as well as aggravated cell cycle arrest and apoptosis resulted from DDP, making pancreatic cancer cells more sensible to DDP. Our results showed that GK921 increased the protein levels regarding E-cadherin as well as decreased the protein level regarding Snail2, N-cadherin, which indicated that GK921 inhibited EMT in pancreatic cancer cells. Snail2 overexpression inhibited GK921/DDP-induced cell apoptosis, as well as mitigated the GK921/DDP-caused cell death and the EMT inhibition. In vivo studies also found GK921/DDP combination can further inhibit the growth of PAAD without significantly side effects. To sum up, we showed that GK921 increased PAAD cells sensitivity to DDP via inhibiting EMT. As revealed, DDP/GK921 co-treatment could promisingly serve for treating PAAD patients.

A zinc metabolism-related gene signature for predicting prognosis and characteristics of breast cancer.

Background: Breast cancer is one of the most serious and prevalent malignancies. Zinc is commonly known to play a crucial role in the development and progression of breast cancer; however, the detailed mechanisms underlying this role are not well understood. This study aimed to develop a zinc metabolism-related gene (ZMRG) signature based on a multi-database study to predict patient prognosis and investigate the relationship between drug therapy response and immune enrichment. Methods: Data for breast cancer samples from The Cancer Genome Atlas and Gene Expression Omnibus databases were screened for zinc metabolism-related genes using the Molecular Signature Database. Cox and Least Absolute Shrinkage and Selection Operator regressions were performed to construct a ZMRG signature. To assess the predictive performance of the gene signature, Kaplan-Meier analysis and receiver operating characteristic curves were used. Additionally, we utilised single-sample gene set enrichment analysis, the Tumour Immune Estimation Resource, the Genomics of Drug Sensitivity in Cancer database, and the Cancer Therapeutics Response Portal to investigate the association between the tumour microenvironment and drug sensitivity. Quantitative PCR was used to assess the expression of each gene in the signature in breast cancer cell lines and patient samples. Results: Five ZMRGs were identified (ATP7B, BGLAP, P2RX4, SLC39A11, and TH) and a risk profile was constructed for each. Two risk groups, high- and low-risk, were identified in this way, and the high-risk score subgroups were found to have worse prognosis. This risk profile was validated using the GSE42568 dataset. Tumour microenvironment and drug sensitivity analyses showed that the expression of these five ZMRGs was significantly associated with immune response. The high-risk group showed substantial immune cell infiltration and enrichment of immune pathways, and patients were more sensitive to drugs commonly used in breast cancer. Conclusion: The ZMRG signature represents a new prognostic predictor for patients with breast cancer, and may also provide new insights into individualised treatment of breast cancer.

The Clinical and Molecular Characteristics of Sex-Determining Region Y-Box 2 and its Prognostic Value in Breast Cancer: A Systematic Meta-Analysis.

OBJECTIVE: Transcription factor SOX2 (sex-determining region Y-box 2) has a crucial role in the maintenance of the stem cell state. However, current evidence regarding the role of SOX2 in breast cancer is conflicting. We conducted this meta-analysis to clarify the association of SOX2 expression with clinical and molecular features and its prognostic effect on breast cancer. METHODS: All relevant articles were searched using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs: multivariate Cox survival analysis) with their 95% confidence intervals (CIs) were calculated. RESULTS: A final total of 18 studies containing 3,080 patients with breast cancer were included. SOX2 protein expression was not related to age, menopausal status, lymph node metastasis, lymphovascular invasion, molecular estrogen receptor status, progesterone receptor status, triple-negative status, and the overall survival in breast cancer, but was closely associated with advanced tumor grade (grade 3 vs. grade 1-2: OR = 2.74, 95% CI = 1.85-4.06, p < 0.001), clinical stage (stage 3-4 vs. stage 0-2: OR = 2.46, 95% CI = 1.37-4.40, p = 0.002), pT stage (T stage 2-4 vs. T stage 1: OR = 1.52, 95% CI = 1.07-2.17, p = 0.019), molecular human epidermal growth factor receptor 2 (HER2) status (positive vs. negative: OR = 1.61, 95% CI = 1.21-2.14, p = 0.001), epidermal growth factor receptor (EGFR) status (positive vs. negative: OR = 2.21, 95% CI = 1.13-4.33, p = 0.021), and worse disease-free survival (DFS) (HR = 2.66, 95% CI = 1.20-5.91, p = 0.016) of breast cancer. CONCLUSIONS: SOX2 expression is correlated with breast cancer progression, HER2 status, and EGFR status, and may be an independent prognostic marker for predicting poor DFS.

Malignant adenomyoepithelioma of the breast: A case report.

RATIONALE: Adenomyoepithelioma (AME) is a rare biphasic tumor consisting of epithelial and Myoepithelial cell. Most of the AME is benign, and only a few will progress to malignancy, Here, we report a case of low-grade malignant adenomyoepithelioma, and review the related literature, in a bid to investigate its clinical and pathological features and thus, enhance our understanding of this tumor. PATIENT CONCERNS: A 64-year-old woman visited our hospital with a 1-year history of a painless mass in her left breast. Physical examination revealed a palpable painless mass, measuring approximately 4.5 cm, in the left breast. DIAGNOSIS: Histological examination confirmed the diagnosis of malignant adenomyoepithelioma. INTERVENTIONS: The patient underwent local excision of the mass, with frozen section analysis revealing ductal carcinoma in situ. Mastectomy and sentinel lymph node biopsy were then performed. OUTCOMES: We conducted a one-year follow-up, and relapse was not observed. LESSONS: Treatment of AME remains controversial owing to the lack of high volume data and absence of prospective studies. Simple mastectomy is an acceptable treatment of this tumor.

Long non-coding RNASNHG17 promotes the progression of breast cancer by sponging miR-124-3p.

BACKGROUND: Small nucleolar RNA host gene 17 (SNHG17), a novel cancer-related long noncoding RNA (lncRNA), was reported to be responsible for processing and developing in several cancers. Nonetheless, the clinical significance and biological function of SNHG17 in human breast cancer (BC) remain rarely known. MATERIALS AND METHODS: 58 pairs of BC tissues and adjacent non-cancerous tissues were harvested to measure SNHG17 expression levels. SNHG17 was knockdown to study its biological behavior in BC cells. The microRNAs (miRNAs) that can bind to SNHG17 were predicated using Starbase2.0 and were tested using luciferase reporter activity and RIP assays. A xenograft model was established to investigate the impact of SNHG17 in tumor growth in vivo. RESULTS: An increased SNHG17 was observed in BC samples and cell lines compared with corresponding control. Increased SNHG17 was closely associated with poor prognosis.SNHG17 depletion suppressed cell proliferation, migration and invasion in vitro, as well as inhibited tumor growth in xenograft tumor models. Mechanistically, SNHG17 could function as an endogenous sponge of miR-124-3p in BC cells. Moreover, the repression of cell proliferation, migration and invasion induced by SNHG17 knockdown would reversed by miR-124-3p inhibitor. CONCLUSION: The present study demonstrated that the lncRNASNHG17 could regulate the progression of BC by sponging miR-124-3p.

Hamartoma of the breast in a man: A rare case report.

RATIONALE: Mammary hamartoma is a rare benign breast tumor, composed of ducts, lobules, fibers, and adipose tissue. We describe a mammary hamartoma in a man; this is the fourth case being reported in the literature. PATIENT CONCERNS: A 30-year-old man presented with a 1-month history of a painless mass in his right breast. DIAGNOSIS: Ultrasound imaging and mammography revealed a lesion, approximately 2.0 cm × 2.0 cm in size, in the right breast, which was considered to be either a lipomyoma or an adenoma fibrosum. INTERVENTIONS: The mass was surgically resected. Pathological examination confirmed the diagnosis of mammary hamartoma. OUTCOMES: The patient was discharged from the hospital after surgery. There was no sign of reoccurrence during a 1-year follow-up period. LESSONS: At present, mammary hamartoma is considered to be a benign lesion, usually treated by surgical resection. Some reports have suggested a possible association between a hamartoma and the development of breast malignancy. The pathology and biology of an association between a mammary hamartoma and malignancy have not been defined to date.

Prevalence of BRCA1 and BRCA2 gene mutations in Chinese patients with high-risk breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Here, we report the prevalence of BRCA1/2 mutations in patients with high-risk breast cancer from Inner Mongolia and Jilin, China, which was a part of a nationwide project on the detection of BRCA1/2 mutations in Chinese patients with hereditary breast cancer. METHODS: According to the criteria, index patients from a total of 245 independent families were initially recruited. All 49 exons of BRCA1 and BRCA2 and adjacent noncoding regions were screened for mutations based on next-generation sequencing from collected saliva. RESULTS: We detected 17 BRCA1/2 variants in 18 of 216 (8.3%) index patients with high-risk breast cancer. Among these, seven mutations were novel, including four BRCA1 mutations (c.123_124delCAinsAT, c.5093_5096delCTAA, c.5396-2A>G, and c.2054delinsGAAGAGTAACAAGTAAGAAGAGTAACAAGAAG), and three BRCA2 mutations (c.304A>T, c.7552_7553insT, and c.9548_9549insA). The BRCA1/2 variants were identified in 14% (8/57) of the patients with triple-negative breast cancer and in 6.3% (10/159) of the patients with non-triple-negative breast cancer. There was no significant difference between the two groups (p = 0.07). A higher frequency for BRCA1 mutations was observed in patients with triple-negative breast cancer than in those with non-triple-negative breast cancer (12.3% vs. 2.5%, p = 0.004). The frequencies of the BRCA2 mutations were not significantly different between patients with triple-negative breast cancer and those with non-triple-negative breast cancer (1.8% vs. 3.8%, p = 0.46). CONCLUSION: We found that patients with triple-negative breast cancer had a higher frequency of BRCA1 mutations than those with non-triple-negative breast cancer. In this study, no significant associations between the BRCA1/2 mutation status and age, family history of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer, number of primary lesions, tumor size, or lymph node metastasis were observed.