Multigene testing panels reveal pathogenic variants in sporadic breast cancer patients in northern China.

Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants.

Outcomes of transsphenoidal surgery in dopamine agonist-resistant prolactinomas: a retrospective study.

PURPOSE: Dopamine agonists (DA) comprise first-line treatment for prolactinomas. However, some patients show no response to DA and are considered resistant. In this study, we retrospectively analyzed the outcomes of DA-resistant prolactinoma patients after transsphenoidal surgery (TSS). METHODS: A total of 94 consecutive patients with DA-resistant prolactinomas who underwent TSS were retrospectively enrolled in the present study. Early postoperative remission rate, prolactin (PRL) levels, and recurrence rate were analyzed. RESULTS: Of 94 DA-resistant patients, 47 (50%) achieved early remission 1 week post-surgery, including 41.18% of macroprolactinoma patients and 73.08% of microprolactinoma patients. PRL levels on the first postoperative day were significantly lower than preoperative PRL levels (p < 0.001). Total resection rate in macro- and microprolactinomas were, respectively, 75 and 96.15%. A recurrence of hyperprolactinemia and tumor was, respectively, found in 31.91 and 19.15% of patients with a follow-up of 39.53 ± 2.172 months (range 3-86). A higher hyperprolactinemia recurrence was observed in patients with invasive prolactinomas (p = 0.021) or preoperative PRL levels ≥ 200 ng/ml (p = 0.029). Univariate logistic regression indicated that larger maximum tumor diameter (p = 0.045), invasive prolactinomas (p = 0.002), and absence of early postoperative remission (p = 0.004) were significant predictors of tumor recurrence. However, using multivariate stepwise logistic regression, only invasiveness and early postoperative remission remained significant. CONCLUSION: Tumor invasiveness and preoperative PRL levels were significant predictors of hyperprolactinemia recurrence after TSS. For tumor recurrence, invasiveness and early postoperative remission were independent predictors.

LncRNA OIP5-AS1 Promotes Breast Cancer Progression by Regulating miR-216a-5p/GLO1.

BACKGROUND: Breast cancer is a familiar malignant tumor, which is a great threat to women's life. Long noncoding RNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) has been reported to be associated with numerous cancers. This study aimed to explore the role of OIP5-AS1 and the mechanism of its action in the progression of breast cancer. METHODS: The expression of OIP5-AS1 and miR-216a-5p was detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, or invasion was assessed by 4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, flow cytometry, or transwell assay, respectively. The binding sites were predicted by bioinformatics tool starBase2.0 (http://starbase.sysu.edu.cn/starbase2/index.php). The interaction between miR-216a-5p and OIP5-AS1 or glyoxalase 1 (GLO1) was confirmed by dual-luciferase reporter assay. The expression of GLO1 was quantified by Western blot. Nude mouse tumorigenicity assays were conducted to verify the role of OIP5-AS1 in vivo. RESULTS: OIP5-AS1 and GLO1 were highly expressed in both clinical tumor tissues and cell lines, whereas miR-216a-5p was downregulated. Knockdown of OIP5-AS1 suppressed proliferation, migration, and invasion but promoted apoptosis of breast cancer cells. MiR-216a-5p was a target of OIP5-AS1 and interacted with GLO1. MiR-216a-5p inhibition or GLO1 overexpression reversed the effects of OIP5-AS1 knockdown on the development of breast cancer cells. OIP5-AS1 knockdown depleted tumor growth in vivo. CONCLUSIONS: OIP5-AS1 knockdown suppressed the progression of breast cancer by inducing GLO1 expression via competitively binding to miR-216a-5p, suggesting that OIP5-AS1 was a hopeful biomarker for the therapy of breast cancer.

Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1-Drp1 pathway.

Activation of the cannabinoid CB1 receptor induces neuroprotection against brain ischemia/reperfusion injury (IRI); however, the mechanism is still unknown. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neuronal cells and middle cerebral artery occlusion (MCAO)-induced brain IRI in rats to mimic ischemic brain injury, and hypothesized that the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) would protect ischemic neurons by inhibiting mitochondrial fission via dynamin-related protein 1 (Drp1). We found that OGD/R injury reduced cell viability and mitochondrial function, increased lactate dehydrogenase (LDH) release, and increased cell apoptosis, and mitochondrial fission. Notably, ACEA significantly abolished the OGD/R-induced neuronal injuries described above. Similarly, ACEA significantly reversed MCAO-induced increases in brain infarct volume, neuronal apoptosis and mitochondrial fission, leading to the recovery of neurological functions. The neuroprotective effects of ACEA were obviously blocked by coadministration of the CB1 receptor antagonist AM251 or by the upregulation of Drp1 expression, indicating that ACEA alleviates brain IRI via the CB1-Drp1 pathway. Our findings suggest that the CB1 receptor links aberrant mitochondrial fission to brain IRI, providing a new therapeutic target for brain IRI treatment.