Correlation of androgen receptor with ultrasound, clinicopathological features and clinical outcomes in breast cancer.

BACKGROUND: This study aimed to explore whether there is an association between androgen receptor (AR) expression and ultrasound, clinicopathological features and prognosis of breast cancer. METHODS: A total of 141 breast cancer patients were included in this retrospective study. AR expression was analyzed by immunohistochemistry. The images of B-mode, color Doppler and strain elastography from 104 patients were collected continuously, and the corresponding ultrasound characteristics were obtained. The differences in ultrasound and clinicopathological features in different AR status were analyzed. Progression-free survival (PFS) of patients was obtained through up to 90 months of follow-up; then, the effect of AR on PFS was analyzed. Subsequently, a nomogram was constructed to predict the AR status. The predictive accuracy was calculated using C-index. RESULTS: The positive expression of AR (AR +) was associated with lower histological grade (p = 0.034) and lower Ki-67 level (p = 0.029). Triple-negative breast cancer (TNBC) had the lowest probability of AR + (p < 0.001). The AR + group mostly showed unsmooth margin (p < 0.001), posterior acoustic shadowing (p = 0.002) and higher elasticity score (p = 0.022) on ultrasound. The echo pattern of most tumors with AR + was heterogeneous (p = 0.024) in Luminal A subtype. AR + could be a sign of a better prognosis in overall breast cancer (p < 0.001), as well as in human epidermal growth factor receptor 2 (HER2) overexpression and Luminal B subtypes (p = 0.001 and 0.025). The nomogram showed relatively reliable performance with a C-index of 0.799. CONCLUSION: Our research demonstrated that AR expression was closely related to ultrasound, clinicopathological features and prognosis of breast cancer.

Radiogenomic analysis of prediction HER2 status in breast cancer by linking ultrasound radiomic feature module with biological functions.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpressed associated with poor prognosis in breast cancer and HER2 has been defined as a therapeutic target for breast cancer treatment. We aimed to explore the molecular biological information in ultrasound radiomic features (URFs) of HER2-positive breast cancer using radiogenomic analysis. Moreover, a radiomics model was developed to predict the status of HER2 in breast cancer. METHODS: This retrospective study included 489 patients who were diagnosed with breast cancer. URFs were extracted from a radiomics analysis set using PyRadiomics. The correlations between differential URFs and HER2-related genes were calculated using Pearson correlation analysis. Functional enrichment of the identified URFs-correlated HER2 positive-specific genes was performed. Lastly, the radiomics model was developed based on the URF-module mined from auxiliary differential URFs to assess the HER2 status of breast cancer. RESULTS: Eight differential URFs (p < 0.05) were identified among the 86 URFs extracted by Pyradiomics. 25 genes that were found to be the most closely associated with URFs. Then, the relevant biological functions of each differential URF were obtained through functional enrichment analysis. Among them, Zone Entropy is related to immune cell activity, which regulate the generation of calcification in breast cancer. The radiomics model based on the Logistic classifier and URF-module showed good discriminative ability (AUC = 0.80, 95% CI). CONCLUSION: We searched for the URFs of HER2-positive breast cancer, and explored the underlying genes and biological functions of these URFs. Furthermore, the radiomics model based on the Logistic classifier and URF-module relatively accurately predicted the HER2 status in breast cancer.

miR-125b-5p upregulation by TRIM28 induces cisplatin resistance in non-small cell lung cancer through CREB1 inhibition.

OBJECTIVE: miR-125b-5p plays an important role in the development of cancer and drug resistance. However, in cisplatin resistance of non-small cell lung cancer (NSCLC), the function and potential mechanism of miR-125b-5p is still unclear. The aim of this study was to investigate the role and molecular mechanism of miR-125b-5p in cisplatin resistance of NSCLC. METHODS: A GEO dataset (GSE168707) was analyzed to find high miR-125b-5p levels were associated with DDP resistance. miR-125b-5p expression levels were detected in A549 and A549/DDP cells via real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays, western blots and mouse model xenografted were performed to identify CREB1 as a direct target gene of miR-125b-5p. Cell proliferation and apoptosis were also performed to identify whether miR-125b-5p upregulation by TRIM28 induces DDP resistance in NSCLC through CREB1 inhibition. RESULTS: In A549/DDP cells, miR-125b-5p expression was upregulated compared to A549 cells. Then miR-125b-5p was found to increase DDP resistance in NSCLC in vivo and in vitro by increasing cell proliferation and suppressing cell apoptosis. Bioinformatic analyses were used to search for gene which miR-125b-5p can target. We identified miR-125b-5p can regulate CREB1 via luciferase reporter assays, qRT-PCR and western blots. Cell proliferation and apoptosis were also performed to confirm miR-125b-5p could impact on CREB1 and induce the DDP resistance in NSCLC. Additionally, we used bioinformatic analyses to find tripartite motif-containing 28 (TRIM28) as a transcriptional enhance factor of miR-125b-5p. The expression of TRIM28 was upregulated in A549/DDP cells compared with that in A549 cells by qRT-PCR. Finally, we found TRIM28 could mediate DDP resistance through miR-125b-5p/CREB1 axis via cell proliferation, western blot and apoptosis assay. CONCLUSIONS: Overall, our findings demonstrated novel functions and mechanisms underlying DDP resistance in NSCLC through the TRIM28/miR-125b-5p/CREB1 axis. These may serve as novel therapeutic targets to improve the treatment efficacy using DDP for NSCLC in the future.

Long-term use of broad-spectrum antibiotics affects Ly6Chi monocyte recruitment and IL-17A and IL-22 production through the gut microbiota in tumor-bearing mice treated with chemotherapy.

The protective effects of antibiotics against infection in cancer patients treated with chemotherapy remains unclear and related studies have been performed in healthy or pathogen-infected animal models. Here, we aimed to study the effects of antibiotic use on intestinal infection in tumor-bearing mice treated with chemotherapy and to determine the underlying mechanisms. Subcutaneous CT26 tumor-bearing mice were assigned to four groups: the control (Ctrl) group without any treatment, the antibiotic (ATB) group treated with a mixture of ampicillin, streptomycin, and colistin, the 5-fluorouracil (FU) group treated with four cycles of intraperitoneal injections of FU, and the ATB + FU group treated with the combination of ATB and FU. Gut microbial composition was determined and mesenteric lymph nodes (mLNs) were isolated for bacterial culturing. Intestinal permeability and integrity were assessed and the expression of cytokines was analyzed by quantitative PCR, ELISA, or flow cytometry (FCM). Monocytes in the colonic lamina propria (LP) were measured by FCM. Compared with the Ctrl and FU groups, the numbers of positive bacterial culturing results for mLNs were higher, and gut bacterial compositions were altered in the ATB and ATB + FU groups, with significantly decreased alpha diversity in the ATB + FU group. Intestinal integrity regarding the expression of tight junction proteins and intestinal permeability were not impaired significantly after treatments, but the colons were shorter in the ATB + FU group. The expression levels of intestinal IL-17A and IL-22, as well as the percentages of IL-17A+ cells in the colonic LP of the ATB + FU group, were lower than those in the FU group. The percentages of Ly6Chi monocytes in the colonic LP were lower, but those in the spleen were higher in the ATB + FU group than in the FU group. The mRNA levels of colonic CCL8 were reduced in the ATB + FU group. Antibiotic use is associated with an increased incidence of intestinal infections in tumor-bearing mice treated with chemotherapy, which might in turn be associated with a dysregulated gut microbiota that inhibits colonic monocyte recruitment and IL-17A and IL-22 production.

Nomograms predicting recurrence in patients with triple negative breast cancer based on ultrasound and clinicopathological features.

OBJECTIVES: The clinicopathological and ultrasound features associated with recurrence in patients with triple negative breast cancer (TNBC) were used to develop a nomogram to predict the prognosis of TNBC. METHODS: Clinicopathological data of 300 patients with TNBC treated between July 2012 and September 2014 were retrospectively reviewed. The endpoint was progression-free survival (PFS). Prognostic factors were screened by multivariate COX regression to develop nomograms. The C-index and calibration curves were used to evaluate the predictive accuracy and discriminatory ability of nomograms. RESULTS: Of 300 patients with TNBC followed-up for 5 years, 80 (26.7%) had PFS events. Five informative prognostic factors (large size, vertical orientation, posterior acoustic enhancement, lymph node involvement, and high pathological stage) were screened and used to construct a nomogram for PFS. The C-index of the PFS nomogram was 0.88 (p < 0.01, 95% confidence interval, 0.85-0.90), indicating good predictive accuracy. CONCLUSIONS: We developed and validated a nomogram for predicting PFS in TNBC. Vertical orientation and posterior acoustic enhancement in ultrasound images of TNBC were associated with worse outcomes. ADVANCES IN KNOWLEDGE: Patients with TNBC have a very poor prognosis and patients have a high risk of recurrence, and our study developed a nomogram based on ultrasound and clinicopathological features for TNBC patients to improve the accuracy of individualized prediction of recurrence and provide help for clinical treatment.

Predicting Pathological Complete Response After Neoadjuvant Chemotherapy in Advanced Breast Cancer by Ultrasound and Clinicopathological Features Using a Nomogram.

BACKGROUND AND AIMS: Prediction of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer is critical for surgical planning and evaluation of NAC efficacy. The purpose of this project was to assess the efficiency of a novel nomogram based on ultrasound and clinicopathological features for predicting pCR after NAC. METHODS: This retrospective study included 282 patients with advanced breast cancer treated with NAC from two centers. Patients received breast ultrasound before NAC and after two cycles of NAC; and the ultrasound, clinicopathological features and feature changes after two cycles of NAC were recorded. A multivariate logistic regression model was combined with bootstrapping screened for informative features associated with pCR. Then, we constructed two nomograms: an initial-baseline nomogram and a two-cycle response nomogram. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were analyzed. The C-index was used to evaluate predictive accuracy. RESULTS: Sixty (60/282, 21.28%) patients achieved pCR. Triple-negative breast cancer (TNBC) and HER2-amplified types were more likely to obtain pCR. Size shrinkage, posterior acoustic pattern, and elasticity score were identified as independent factors by multivariate logistic regression. In the validation cohort, the two-cycle response nomogram showed better discrimination than the initial-baseline nomogram, with the C-index reaching 0.79. The sensitivity, specificity, and NPV of the two-cycle response nomogram were 0.77, 0.77, and 0.92, respectively. CONCLUSION: The two-cycle response nomogram exhibited satisfactory efficiency, which means that the nomogram was a reliable method to predict pCR after NAC. Size shrinkage after two cycles of NAC was an important in dependent factor in predicting pCR.