ObjectiveTo investigate the expression of CPEB2 in triple-negative breast cancer (TNBC) and its impact on the malignant progression of tumors. MethodsThe expression level of CPEB2 in breast cancer was analyzed through a database, and the differential expression in clinical pathological specimens was verified by immunohistochemical experiments. Stable CPEB2 overexpressing TNBC cell lines were constructed, and CCK-8 and Transwell assays were used to detect the changes in cell phenotypes. Western blot was used to explore the expression of key molecules in the MEK/ERK signaling pathway. ResultsThe expression of CPEB2 in TNBC tissues was significantly lower than that in adjacent tissues (χ2=16.57, P<0.001). Patients with high expression of CPEB2 had a significantly longer overall survival than those with low expression. Overexpression of CPEB2 inhibited the proliferation, migration, and invasion abilities of TNBC cells and the activation of the MEK/ERK signaling pathway. ConclusionThe expression of CPEB2 is downregulated in TNBC. Upregulation of CPEB2 inhibits the proliferation, migration, and invasion of TNBC cells, accompanied by decreased activation of the MEK/ERK pathway (reduced p-MEK and p-ERK levels), suggesting that CPEB2 may participate in the malignant progression of TNBC by regulating the MEK/ERK pathway.

BACKGROUND:Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS:In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS:445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION:The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING:Akeso Biopharma.

Objective: To study the correlation between epidermal growth factor receptor (EGFR) protein expression, copy number variation, and clinicopathological factors and prognosis of patients with breast cancer. Methods: A total of 172 cancer tissue specimens of patients with invasive breast cancer treated in the oncology department of our hospital from January 2017 to December 2019 were selected randomly and 45 normal tissue samples were collected at the same time. The expression level of EGFR protein was determined by immunohistochemistry and the EGFR copy number variation using a four-color probe in breast cancer patients. The correlation between EGFR protein expression and copy number variation and clinicopathological factors was analyzed using a chi(2) test and Fishers exact probability method, and a prognostic analysis was performed using a Cox proportional hazards multi-factor regression model. Results: The positive expression of EGFR in breast cancer tissues was significantly higher than that in normal tissues (p<0.05). EGFR protein expression had no correlation with age, histological grade, lymph node metastasis, and human epidermal growth factor receptor 2 (HER2) expression (p>0.05), but was notably associated with tumor size, estrogen receptors (ER), progesterone receptors (PR), and molecular subtype (p<0.05). The Cox regression curve model showed that tissue grading, lymphatic metastasis, molecular subtypes, and EGFR positive expression are all independent risk factors affecting the prognosis of breast cancer patients. Among the breast cancer patients, 113 cases (65.7%) had low EGFR copy number variation, including 66 cases of disomy (38.37%), six cases of low trisomy (3.49%), four cases of high trisomy (2.33%), and 37 cases of low polysomy (21.51%); 59 cases (34.3%) had high EGFR copy number variation, including 54 cases of high polysomy (31.4%) and five cases of gene amplification (2.9%). EGFR copy number variation had no significant correlation with age, tumor size, histological grade, lymph node metastasis, and other clinical pathological factors in breast cancer patients (p>0.05). Through the analysis of Cox multi-factor models, high copy number variation of EGFR gene and tissue grade can be used as independent prognostic indicators affecting breast cancer patients. Conclusion: The expression of EGFR protein in breast cancer tissues is significantly higher than that in normal tissues. EGFR protein is an independent risk factor that affects the clinical and pathological characteristics of breast cancer, but the high copy number variation of EGFR gene has no obvious correlation with the clinical case factors of patients. The positive expression of EGFR and the high copy number variation of EGFR are closely related to the prognosis of patients, and can be used as important indicators in evaluating the diagnosis and prognosis of breast cancer patients.

Radiotherapy plays important roles in the treatment of breast cancer (BC), which develops from malignant cells in the breast. Long non-coding RNAs (lncRNAs) have been reported to be implicated in radio-resistance or radio-sensitivity of human cancer, which includes breast cancer. Nevertheless, long intergenic non-protein coding RNA 0504 (LINC00504) has not been investigated in BC. In our study, from RT-qPCR analysis, LINC00504 was found to be up-regulated in BC cells. By conducting in vitro assays, it was confirmed that the knockdown of LINC00504 could enhance the radio-sensitivity of BC cells. The regulatory mechanism of LINC00504 in BC was also verified by chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP) and luciferase reporter assays. From the experimental results, we knew that the up-regulation of LINC00504 was mediated by signal transducer and activator of transcription 1 (STAT1). Moreover, LINC00504 stabilized the expression of cytoplasmic polyadenylation element-binding protein 2 (CPEB2) via binding to TATA-box binding protein associated factor 15 (TAF15). Furthermore, rescue assays validated that LINC00504 participated in regulating the radio-sensitivity of BC cells via up-regulating CPEB2. In summary, our study disclosed that STAT1 could mediate LINC00504 and weaken the radio-sensitivity of BC cells via binding to TAF15 and stabilizing CPEB2 expression.

Objectives-The purpose of this study was to assess the diagnostic performance of ultrasound-guided diffuse optical tomography for differentiation of benign and malignant breast lesions.Methods-The Cochrane Library, PubMed, and Embase databases were searched from inception to February 14, 2016. Sensitivity, specificity, and other information were extracted from the included studies. Sensitivity and specificity were pooled by a bivariate mixed-effects binary regression model. A summary receiver operating characteristic curve was constructed. Heterogeneity and publication bias were explored by Higgins and Deeks tests, respectively.Results-Seven studies including 768 women with 886 lesions were analyzed. The summary sensitivity, specificity, and diagnostic odds ratio were 95% (95% confidence interval [CI], 85%-98%), 77% (95% CI, 66%-85%), and 57 (95% CI, 12-267), respectively. The area under the summary receiver operating characteristic curve was 91% (95% CI, 89%-94%). No significant heterogeneity or publication bias existed.Conclusions-Ultrasound-guided diffuse optical tomography is useful for differentiating breast lesions. Especially, its sensitivity is excellent.