Risk assessment model based on nucleotide metabolism-related genes highlights SLC27A2 as a potential therapeutic target in breast cancer.

PURPOSE: Breast cancer (BC) is the most prevalent malignant tumor worldwide among women, with the highest incidence rate. The mechanisms underlying nucleotide metabolism on biological functions in BC remain incompletely elucidated. MATERIALS AND METHODS: We harnessed differentially expressed nucleotide metabolism-related genes from The Cancer Genome Atlas-BRCA, constructing a prognostic risk model through univariate Cox regression and LASSO regression analyses. A validation set and the GSE7390 dataset were used to validate the risk model. Clinical relevance, survival and prognosis, immune infiltration, functional enrichment, and drug sensitivity analyses were conducted. RESULTS: Our findings identified four signature genes (DCTPP1, IFNG, SLC27A2, and MYH3) as nucleotide metabolism-related prognostic genes. Subsequently, patients were stratified into high- and low-risk groups, revealing the risk model's independence as a prognostic factor. Nomogram calibration underscored superior prediction accuracy. Gene Set Variation Analysis (GSVA) uncovered activated pathways in low-risk cohorts and mobilized pathways in high-risk cohorts. Distinctions in immune cells were noted between risk cohorts. Subsequent experiments validated that reducing SLC27A2 expression in BC cell lines or using the SLC27A2 inhibitor, Lipofermata, effectively inhibited tumor growth. CONCLUSIONS: We pinpointed four nucleotide metabolism-related prognostic genes, demonstrating promising accuracy as a risk prediction tool for patients with BC. SLC27A2 appears to be a potential therapeutic target for BC among these genes.

Authentication of a survival nomogram for non-invasive micropapillary breast cancer.

Purpose: We aimed at establishing a nomogram to accurately predict the overall survival (OS) of non-metastatic invasive micropapillary breast carcinoma (IMPC). Methods: In the training cohort, data from 429 patients with non-metastatic IMPC were obtained through the Surveillance, Epidemiology, and End Results (SEER) database. Other 102 patients were enrolled at the Xijing Hospital as validation cohort. Independent risk factors affecting OS were ascertained using univariate and multivariate Cox regression. A nomogram was established to predict OS at 3, 5 and 8 years. The concordance index (C-index), the area under a receiver operating characteristic (ROC) curve and calibration curves were utilized to assess calibration, discrimination and predictive accuracy. Finally, the nomogram was utilized to stratify the risk. The OS between groups was compared through Kaplan-Meier survival curves. Results: The multivariate analyses revealed that race (p = 0.047), surgery (p = 0.003), positive lymph nodes (p = 0.027), T stage (p = 0.045) and estrogen receptors (p = 0.019) were independent prognostic risk factors. The C-index was 0.766 (95% CI, 0.682-0.850) in the training cohort and 0.694 (95% CI, 0.527-0.861) in the validation cohort. Furthermore, the predicted OS was consistent with actual observation. The AUCs for OS at 3, 5 and 8 years were 0.786 (95% CI: 0.656-0.916), 0.791 (95% CI: 0.669-0.912), and 0.774 (95% CI: 0.688-0.860) in the training cohort, respectively. The area under the curves (AUCs) for OS at 3, 5 and 8 years were 0.653 (95% CI: 0.498-0.808), 0.683 (95% CI: 0.546-0.820), and 0.716 (95% CI: 0.595-0.836) in the validation cohort, respectively. The Kaplan-Meier survival curves revealed a significant different OS between groups in both cohorts (p<0.001). Conclusion: Our novel prognostic nomogram for non-metastatic IMPC patients achieved a good level of accuracy in both cohorts and could be used to optimize the treatment based on the individual risk factors.

A novel tool for improving the accuracy of major depressive disorder screening: A prospective study on andrology with external validation.

Patient Health Questionnaire-9 (PHQ-9) is the most widely used tool for screening for major depressive disorder (MDD). Although its reliability and validity have been proven, missed or misjudged cases during MDD screening are often encountered. A nomogram that considers the weights of depressive symptoms was developed using data from premature ejaculation patients to improve screening accuracy. During a 33-month prospective study, a training cohort comprising 605 participants from Xijing Hospital was used to develop and internally validate the nomogram. A validation cohort comprising 461 patients from Xi'an Daxing Hospital was also used to externally test the nomogram. The nomogram was established by integrating the LASSO regression-based optimal predictors of MDD according to their coefficients in a multivariate logistic regression model. The nomogram was well-calibrated during internal and external validations. Moreover, it showed a better discriminatory capacity and yielded more net benefits in both validations than PHQ-9. With better performance, the nomogram may help reduce the number of missed or misjudged cases during MDD screening. This study is the first to weigh the direct indicators of MDD under the DSM-5 criteria, presenting a fresh concept that can be applied to other populations to enhance screening accuracy.

PRMT5 reduces immunotherapy efficacy in triple-negative breast cancer by methylating KEAP1 and inhibiting ferroptosis.

BACKGROUND: As an emerging treatment strategy for triple-negative breast cancer (TNBC), immunotherapy acts in part by inducing ferroptosis. Recent studies have shown that protein arginine methyltransferase 5 (PRMT5) has distinct roles in immunotherapy among multiple cancers by modulating the tumor microenvironment. However, the role of PRMT5 during ferroptosis, especially for TNBC immunotherapy, is unclear. METHODS: PRMT5 expression in TNBC was measured by IHC (immunohistochemistry) staining. To explore the function of PRMT5 in ferroptosis inducers and immunotherapy, functional experiments were conducted. A panel of biochemical assays was used to discover potential mechanisms. RESULTS: PRMT5 promoted ferroptosis resistance in TNBC but impaired ferroptosis resistance in non-TNBC. Mechanistically, PRMT5 selectively methylated KEAP1 and thereby downregulated NRF2 and its downstream targets which can be divided into two groups: pro-ferroptosis and anti-ferroptosis. We found that the cellular ferrous level might be a critical factor in determining cell fate as NRF2 changes. In the context of higher ferrous concentrations in TNBC cells, PRMT5 inhibited the NRF2/HMOX1 pathway and slowed the import of ferrous. In addition, a high PRMT5 protein level indicated strong resistance of TNBC to immunotherapy, and PRMT5 inhibitors potentiated the therapeutic efficacy of immunotherapy. CONCLUSIONS: Our results reveal that the activation of PRMT5 can modulate iron metabolism and drive resistance to ferroptosis inducers and immunotherapy. Accordingly, PRMT5 can be used as a target to change the immune resistance of TNBC.

Development of a predictive risk stratification tool to identify the population over age 45 at risk for new-onset stroke within 7 years.

Background and purpose: With the acceleration of the aging process of society, stroke has become a major health problem in the middle-aged and elderly population. A number of new stroke risk factors have been recently found. It is necessary to develop a predictive risk stratification tool using multidimensional risk factors to identify people at high risk for stroke. Methods: The study included 5,844 people (age ≥ 45 years) who participated in the China Health and Retirement Longitudinal Study in 2011 and its follow-up up to 2018. The population samples were divided into training set and validation set according to 1:1. A LASSO Cox screening was performed to identify the predictors of new-onset stroke. A nomogram was developed, and the population was stratified according to the score calculated through the X-tile program. Internal and external verifications of the nomogram were performed by ROC and calibration curves, and the Kaplan-Meier method was applied to identify the performance of the risk stratification system. Results: The LASSO Cox regression screened out 13 candidate predictors from 50 risk factors. Finally, nine predictors, including low physical performance and the triglyceride-glucose index, were included in the nomogram. The nomogram's overall performance was good in both internal and external validations (AUCs at 3-, 5-, and 7-year periods were 0.71, 0.71, and 0.71 in the training set and 0.67, 0.65, and 0.66 in the validation set, respectively). The nomogram was proven to excellently discriminate between the low-, moderate-, and high-risk groups, with a prevalence of 7-year new-onset stroke of 3.36, 8.32, and 20.13%, respectively (P < 0.001). Conclusion: This research developed a clinical predictive risk stratification tool that can effectively identify the different risks of new-onset stroke in 7 years in the middle-aged and elderly Chinese population.

Effects and differences of sleep duration on the risk of new-onset chronic disease conditions in middle-aged and elderly populations.

BACKGROUND: Few longitude cohort studies investigated the risk of the duration of nighttime sleep and naps to the new-onset common chronic disease conditions (CDCs) in middle-aged (45-60) and the elderly (age ≥ 60) populations using an age-stratified strategy. METHODS: The 7025 participants from The China Health and Retirement Longitudinal Study were screened as eligible subjects. Established 13 cohorts with CDCs, acquired their' sleep records in 2011, and obtained new-onset incidents of CDCs during follow-up in 2011-2018. Performed risk association analyses between sleep duration and 13 new-onset CDCs respectively. RESULTS: New-onset risk of four CDCs decreased with increasing nighttime sleep (p-nonlinear>0.05). The risk threshold was approximately 7 hours in middle-aged people and 6 hours in the elderly. For the middle-aged population, compared with 7-9hours sleep, <5hour and 5-7hours nighttime sleep were associated with 1.312∼1.675 times more risk of hypertension, kidney disease, diabetes or high blood sugar status, and multimorbidity; Compared with no nap, a 0-30 min nap was associated with 1.413(1.087∼1.837) times the heart disease risk. In the elderly, < 5 hours of night sleep was a significant risk factor for four CDCs including kidney disease and multimorbidity, etc. A long night's sleep (>9 hours) was connected with 61.2% reduction in risk of memory disease, a >90 min nap increased 62% risk of memory disease, and a 0-30 min nap was associated with higher risks of heart disease, hypertension, and a lower kidney disease risk. CONCLUSIONS: Nighttime sleep and daytime naps may have their own implications for the new-onset CDCs' risk in the aging process.

Association of the depressive scores, depressive symptoms, and conversion patterns of depressive symptoms with the risk of new-onset chronic diseases and multimorbidity in the middle-aged and elderly Chinese population.

Background: The relationship between depressive symptoms (DS) and their conversion patterns over time and the new-onset risk of diseases in the middle-aged and elderly population has not been extensively studied. Methods: Based on The China Health and Retirement Longitudinal Study participants in 2013, we established 13 cohorts involving 12 types of chronic diseases and multimorbidity, who were identified by face-to-face questionnaires. We retrospectively assessed their DS during 2011 and 2013 through the 10-item Center for Epidemiological Studies Depression Scale (CES-D), which were classified into never, newly developed, relieved, and persistent DS, and these participants were followed from 2013 to 2018. Findings: CES-D scores were new-onset risk factors for 9 diseases. The new-onset risk of diseases increased with higher CES-D scores. When CES-D scores were higher than approximately 6, the hazard ratios (HRs) of emergent diseases were greater than 1. DS was independent new-onset risk factors for 8 diseases, with HRs (95% CI) ranging from 1.2635 (1.0061-1.5867) to 1.5231 (1.0717-2.165). Persistent DS was an independent risk factor for most diseases but might be an independent protective factor for new-onset cancer (HR, 95% CI: 0.276, 0.106-0.723). Interpretation: DS is closely associated with new-onset risk of chronic diseases and multimorbidity, and awareness of the risk associated with pre-DS status (6

A Prospectively Validated Nomogram for Predicting the Risk of PHQ-9 Score ≥15 in Patients With Erectile Dysfunction: A Multi-Center Study.

Background: Although erectile dysfunction (ED) often occurs simultaneously with depression, not all patients with ED suffer major depression (MD), with a PHQ-9 score ≥15 indicating MD. Because the PHQ-9 questionnaire includes phrases such as "I think I am a loser" and "I want to commit suicide," the psychological burdens of ED patients are likely to increase inevitably after using the PHQ-9, which, in turn, may affect ED therapeutic effects. Accordingly, we endeavored to develop a nomogram to predict individual risk of PHQ-9 score ≥15 in these patients. Methods: The data of 1,142 patients with ED diagnosed in Xijing Hospital and Northwest Women and Children's Hospital from January 2017 to May 2020 were analyzed. While the Least Absolute Shrinkage and Selection Operator regression was employed to screen PHQ-9 score ≥15 related risk factors, multivariate logistic regression analysis was performed to verify these factors and construct the nomogram. The training cohort and an independent cohort that comprised 877 prospectively enrolled patients were used to demonstrate the efficacy of the nomogram. Results: The IIEF-5 score, PEDT score, physical pain score, frequent urination, and feeling of endless urination were found to be independent factors of PHQ-9 score ≥15 in patients with ED. The nomogram developed by these five factors showed good calibration and discrimination in internal and external validation, with a predictive accuracy of 0.757 and 0.722, respectively. The sensitivity and specificity of the nomogram in the training cohort were 0.86 and 0.52, respectively. Besides, the sensitivity and specificity of the nomogram in the validation cohort were 0.73 and 0.62, respectively. Moreover, based on the nomogram, the sample was divided into low-risk and high-risk groups. Conclusion: This study established a nomogram to predict individual risk of PHQ-9 score ≥15 in patients with ED. It is deemed that the nomogram may be employed initially to avoid those with a low risk of MD completing questionnaires unnecessarily.

Nomogram for stratifying patients with lifelong premature ejaculation before using the PHQ-9: An observational study.

OBJECTIVE: A PHQ-9 score ≥ 15, represented as PHQ-9+ , indicates major depressive disorder (MDD). On using PHQ-9, the psychological burden of several patients with lifelong premature ejaculation (LPE) gets aggravated, which may lead to LPE development. We aim to construct a nomogram for predicting the individual risk of PHQ-9+ in patients with LPE and discerning those with low risks, who should avoid the PHQ-9. METHODS: The nomogram was constructed by analysing data of 802 patients from Xijing Hospital and Northwest Women's & Children's Hospital. The LASSO and multivariable logistic regressions were used to identify independent predictors of PHQ-9+ , used for developing the nomogram. The discrimination, calibration and clinical usefulness of the nomogram were assessed in the derivation cohort and an independent validation cohort, which was composed of 505 prospectively enrolled patients from Daxing Hospital and Xijing Hospital. RESULTS: The duration of PE, IELT, a history of PE exacerbation, IIEF-5 score, urinary frequency and physical pain score were identified as independent predictors. The nomogram showed excellent calibration, discrimination and clinical usefulness in the derivation and validation cohorts, with a predictive accuracy of 0.781 and 0.763, respectively. Based on this nomogram, patients were divided into not recommended, recommended and strongly recommended PHQ-9 filling groups, with PHQ-9+ rates of 3.5%, 9.3% and 30.7%, respectively. CONCLUSION: A nomogram to discern LPE patients with low risks of PHQ-9+ was established. This tool can increase the positivity of MDD screening and may improve the therapeutic outcomes of those in the low-risk group.

PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer.

Cancer cells respond to various stressful conditions through the dynamic regulation of RNA m6A modification. Doxorubicin is a widely used chemotherapeutic drug that induces DNA damage. It is interesting to know whether cancer cells regulate the DNA damage response and doxorubicin sensitivity through RNA m6A modification. Here, we found that doxorubicin treatment significantly induced RNA m6A methylation in breast cancer cells in both a dose- and a time-dependent manner. However, protein arginine methyltransferase 5 (PRMT5) inhibited RNA m6A modification under doxorubicin treatment by enhancing the nuclear translocation of the RNA demethylase AlkB homolog 5 (ALKBH5), which was previously believed to be exclusively localized in the nucleus. Then, ALKBH5 removed the m6A methylation of BRCA1 for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells. Importantly, we identified the approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methylation and increase doxorubicin sensitivity in breast cancer. The strategy of targeting PRMT5 with tadalafil is a promising approach to promote breast cancer sensitivity to doxorubicin through RNA methylation regulation.

The first competing risk survival nomogram in patients with papillary renal cell carcinoma.

There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUCt of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.

A Prognostic Risk Stratification Model to Identify Potential Population Benefiting From Postmastectomy Radiotherapy in T1-2 Breast Cancer With 1-3 Positive Axillary Lymph Nodes.

BACKGROUND AND OBJECTIVES: To establish a prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT). METHODS: A population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups. RESULTS: The overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P<0.001). In the high-risk group, PMRT can significantly better OS with 10-year all-cause mortality reduced by 6.7% (P = 0.027). However, there was no significant survival difference between PMRT cohort and control cohort in low-risk (P=0.49) and moderate-risk groups (P = 0.35). CONCLUSION: The current study developed the first prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive axillary lymph nodes and found that patients in the high-risk group may be easier to benefit from PMRT.

Development and validation of a risk stratification nomogram for predicting prognosis in bone metastatic breast cancer: A population-based study.

ABSTRACT: Bone metastasis seriously affects the survival of breast cancer. Therefore, the study aimed to explore the independent prognostic factors in bone metastatic breast cancer (BMBC) and to construct a prognostic nomogram that can accurately predict the survival of BMBC and strictly divide the patients into different risk stratification.Four thousand three hundred seventy six patients with BMBC from the surveillance, epidemiology, and end results database in 2010 to 2015 were collected and randomly divided into training and validation cohort. Multivariate Cox regression identified the independent prognostic factors of BMBC. A nomogram for predicting cancer-specific survival (CSS) in BMBC was created using R software. The predictive performance of the nomogram was evaluated by plotting receiver operating characteristic (ROC) curves and calibration curves.Marital status, race, age, T stage, tumor grade, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, brain metastasis, liver metastasis, lung metastasis, chemotherapy, and breast surgery were identified as independent prognostic factors for CSS of BMBC. The area under the ROC curve at 1-, 3-, and 5-year of the nomogram were 0.775, 0.756, and 0.717 in the internal validation and 0.785, 0.737, and 0.735 in the external validation, respectively. Calibration curves further confirmed the unbiased prediction of the model. Kaplan-Meier analysis verified the excellent risk stratification of our model.The first prognostic nomogram for BMBC constructed in our study can accurately predict the survival of BMBC, which may provide a practical tool to help clinicians evaluate prognosis and stratify the prognostic risk for BMBC, thereby determining which patients should be given intensive treatment and optimizing individual treatment strategies for BMBC.

Novel survival nomograms for patients with lung metastatic clear cell renal cell carcinoma: A population-based study.

ABSTRACT: Survival heterogeneity is observed among renal cell carcinoma (RCC) patients with metastases in different organs. Moreover, almost all previous prognostic nomograms based on data from metastatic RCC patients did not take competing events, such as death from cerebrovascular and heart diseases, into account. We aimed to construct novel prognostic nomograms for patients with lung metastatic clear cell RCC (LMCCRCC).Data of 712 non-Hispanic white LMCCRCC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Nomograms for predicting overall survival (OS) and disease-specific survival (DSS) were established using the Cox approach and Fine and Gray approach, respectively, and their performances were assessed using the concordance index (C-index), calibration plots, and an independent cohort comprising 181 Hispanic patients.Sex, tumor grade, T stage, N stage, presence or absence of bone metastases, and presence or absence of brain metastases were independent predictors for both OS and DSS. Additionally, presence or absence of liver metastases was an independent predictor only for DSS. Meanwhile, age at diagnosis was independently associated with OS. The C-indexes of the nomograms were 0.702 for OS and 0.723 for DSS in internal validation. In external validation, the C-indexes were 0.700 for OS and 0.708 for DSS. Both internal and external calibration plots showed excellent consistency between the prediction and the observation.The current study developed a novel nomogram for predicting individual OS in LMCCRCC patients. Moreover, we constructed an effective competing risk nomogram for predicting their individual DSS for the first time.

A novel nomogram predicting the risk of positive biopsy for patients in the diagnostic gray area of prostate cancer.

The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.

Development and Validation of a Nomogram for Individually Predicting Pathologic Complete Remission After Preoperative Chemotherapy in Chinese Breast Cancer: A Population-Based Study.

PURPOSE: To explore the independent predictors of pathologic complete remission response (pCR) for Chinese patients with breast cancer (BC) after preoperative chemotherapy and to develop an individualized nomogram for predicting the probability of pCR. PATIENTS AND METHODS: The clinicopathologic data of clinical stage I-III BC patients who received preoperative chemotherapy in Xijing Hospital were retrospectively analyzed. A total of 689 BC patients diagnosed in 2015-2017 were included in the training set to develop a nomogram. A separate cohort of 357 patients in the same center was regarded as a validation set for externally examining the performance of the model. The area under the receiver operating characteristic curve and calibration curve were used to verify the predictive performance of the nomogram. RESULTS: Multivariate logistic regression analysis showed that independent predictors of pCR were menopause status at diagnosis, family history of BC, initial tumor size, estrogen receptor status, HER2/neu (human epidermal growth factor receptor 2) status, and Ki-67 expression. On the basis of these factors, a nomogram was developed using R software. Our nomogram had good discrimination in the training and validation set (area under the receiver operating characteristic curve, 0.762 and 0.768, respectively). The calibration curves further confirmed that the model performs well. CONCLUSION: Menopause status and family history of BC were independent predictors of pCR after preoperative chemotherapy for the first time. The nomogram can accurately predict pCR rate in BC, which may provide some guidelines for breast surgery options and patient counseling.

Construction and validation of a novel prognostic nomogram for patients with sarcomatoid renal cell carcinoma: a SEER-based study.

OBJECTIVE: The only one established prognostic nomogram for patients with sarcomatoid renal cell carcinoma (sRCC) was based on a small sample-sized study without external validation, and a nomogram can be applied to western sRCC patients has not yet been developed. Therefore, our study aimed to construct and validate an effective nomogram to predict overall survival (OS) for these patients. METHODS: The independent predictors for OS were identified and the nomogram was constructed on the basis of a retrospective study of a training cohort consisted of 428 non-Hispanic white sRCC patients registered in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. Then, the discriminative performance of the nomogram was assessed by the concordance index (C-index). OS calibrations of the nomogram were also performed by comparing the nomogram-predicted probability to the observed survival rate. Furthermore, our nomogram was externally validated using two independent cohorts consisted of 71 non-Hispanic black patients and 82 Hispanic patients, respectively. RESULTS: Age at diagnosis, T stage, N stage, bone metastases, liver metastases, lung metastases and nephrectomy were identified as independent predictors for OS. In the training cohort and two validation cohorts, the C-indexes of the nomogram were 0.737, 0.801 and 0.764, respectively. Besides, excellent agreements between the nomogram prediction and the actual observation were achieved in all cohorts. CONCLUSIONS: The current study constructed and validated an effective prognostic nomogram for patients with sRCC, which can be used to perform accurate predictions of the 0.5-, 1-, and 2-year possibilities of OS.

Compound C enhances the anticancer effect of aspirin in HER-2-positive breast cancer by regulating lipid metabolism in an AMPK-independent pathway.

Various clinical studies have determined that aspirin shows anticancer effects in many human malignant cancers, including human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. However, the anti-tumor mechanism of aspirin has not been fully defined. The aim of this study was to determine the role of Compound C in enhancing the anticancer effect of aspirin. HER-2-positive breast cancer cell lines were treated with aspirin with or without Compound C pre-treatment; their phenotypes and mechanisms were then analyzed in vitro and in vivo. Aspirin exhibited anticancer effects in HER-2-positive breast cancer by inhibiting cell growth and inducing apoptosis through the activation of AMP-activated protein kinase (AMPK). Unexpectedly, pre-treatment with Compound C, a widely used AMPK inhibitor, induced robust anticancer effects in cells compared to aspirin monotherapy. This anticancer effect was not distinct in HER-2 negative breast cancer MDA-MB-231 cells and may be due to the inhibition of lipid metabolism mediated by c-myc. Besides, c-myc re-expression or palmitic acid supply could partially restored cell proliferation. Aspirin exhibits anticancer effects in HER-2-positive breast cancer by regulating lipid metabolism mediated by c-myc, and Compound C strengthens these effects in an AMPK-independent manner. Our results potentially provide a novel therapeutic strategy exploiting combined aspirin and Compound C therapy for HER-2-positive breast cancer, which acts by reducing de novo lipid synthesis.