Analysis of the Relationship Between Primary Tumor Site and Clinicopathological Characteristics and Survival Prognosis of Breast Cancer Patients Based on SEER Database.

PURPOSE: This study aimed to analyze the association between the primary tumor site and clinicopathological characteristics and survival prognosis of breast cancer (BC) patients using a large population database. METHODS: BC patients screened in the Surveillance, Epidemiology, and End Results (SEER) database were categorized into 6 groups based on primary sites. Descriptive statistics, Kaplan-Meier curves, Cox regression models, forest plots were used to assess the effect of primary sites on overall survival (OS) and breast cancer-specific survival (BCSS). Multivariate Cox proportional analyses were conducted to calculate hazard ratios (HRs) and adjusted subgroups' hazard ratios (AHRs). Nomograms were utilized to predict OS and BCSS. RESULTS: Among 193,043 BC patients, the highest incidence was found in the upper outer quadrant (52.60%). Central portion patients are associated with more clinical features indicating a poor prognosis, and had worse OS and BCSS than other sites. Univariate and multifactorial Cox analyses showed associations between OS/BCSS and various factors. Subgroup analyses revealed differences in OS and BCSS between central portion and upper outer quadrant varied among age, T and N stage. The nomogram was established to predict the survival of central portion BC patients. CONCLUSIONS: Primary tumor site is associated with clinicopathological features and prognosis of BC, may be influenced by age at diagnosis and T and N stage. Central portion BC patients have worse prognosis due to older age at diagnosis, higher T stage and higher likelihood of lymph node metastasis. Early diagnosis and treatment may help to improve survival of central portion BC.

Evaluation of neoadjuvant chemotherapy for clinical T1 triple-negative breast cancer.

The role of neoadjuvant chemotherapy and its benefits in patients with triple-negative breast cancer (TNBC) and small tumors are unclear. This study aims to compare survival differences between clinical T1 TNBC receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Data for patients with clinical T1 TNBC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized according to whether they received chemotherapy before or after surgery. Propensity Score Matching (PSM) was used to minimize the influence of confounding factors. OS and BCSS were compared between the two treatment sequences using Kaplan-Meier and univariate and multivariable Cox proportional hazards regression analyses. The study included 6249 women with T1 TNBC. In multivariate analysis, compared with that in the AC group, the hazard ratio for death in the NAC group was 1.54 (95% confidence interval 1.26-1.89, p < 0.001). NAC offers no additional benefits in any age group or T, N subgroups. Our findings suggest that NAC does not provide additional benefit to patients with clinical T1 TNBC, even in the presence of lymph node metastasis, or T1c.

Integrated pan-cancer analysis and experimental verification of the roles of meiotic nuclear divisions 1 in breast cancer.

INTRODUCTION: The aberrant up-regulation of meiotic nuclear division 1 (MND1) in somatic cells is considered as one of the driving factors of oncogenesis, whereas its expression and role in breast invasive cancer (BRCA) remain unclear. Hence, this study embarked on a comprehensive evaluation of MND1 across various cancers and identified its roles in BRCA. METHODS: Based on publicly available databases, including but not limited to UCSC Xena, TCGA, GTEx, GEO, STRING, GeneMANIA, and CancerSEA, we evaluated the expression patterns, genomic features, and biological functions of MND1 from a pan-cancer viewpoint and delved into the implications of MND1 in the prognosis and treatment of BRCA. Further molecular biology experiments were undertaken to identify the role of MND1 in proliferation, migration, and apoptosis in BRCA cells. RESULTS: Elevated levels of MND1 were notably observed in a wide array of tumor types, especially in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, STAD, and UCEC. Elevated MND1 expression was markedly associated with shortened OS in several tumors, including BRCA (HR = 1.52 [95%CI, 1.10-2.09], P = 0.011). The up-regulation of MND1 in BRCA was validated in external cohorts and clinical samples. Survival analyses demonstrated that elevated MND1 expression was associated with decreased survival for patients with BRCA. Co-expressed genes of MND1 were identified, and subsequent pathway analyses based on significantly associated genes indicated that MND1 plays key roles in DNA replication, cell cycle regulation, and DNA damage repair. The observed abnormal elevation and activation of MND1 led to increased proliferation and migration, along with decreased apoptosis in BRCA cells. CONCLUSIONS: MND1 emerges as a promising biomarker for diagnostic and therapeutic targeting in various cancers, including BRCA. The abnormal up-regulation and activation of MND1 are linked to carcinogenesis and poor prognosis among BRCA patients, which may be attributed to its involvement in HR-dependent ALT, warranting further scrutiny.

Impact of response to neoadjuvant chemotherapy on surgical modality in patients with T1-2N0-1M0 triple-negative breast cancer.

PURPOSE: Many T1-2N0-1M0 triple-negative breast cancer (TNBC) patients who undergo neoadjuvant chemotherapy (NAC) do not receive breast-conserving therapy (BCT) due to concerns about non-pCR or lymph node metastasis presence. METHODS: T1-2N0-1M0 TNBC patients who underwent NAC between 2010 and 2017 were collected from the SEER database. Factors affecting surgical modalities were analyzed by multinomial logistic regression. The overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated by Kaplan-Meier curves and Cox proportional hazards models. Further stratified subgroup analyses were performed based on the response to NAC and N-stage. Adjusted-hazard ratios were also calculated to exclude potential bias. RESULTS: A total of 1112 patients were enrolled (median follow-up: 81 months), 58.5% received BCT, 23.6% received reconstruction and 17.9% received mastectomy. Response to NAC and N-stage not only influenced the choice of surgical modality but also were independent predictors for OS and BCSS. The surgery-induced survival differences mainly affect OS. Survival analyses demonstrated that the 10-year OS of BCT was superior or equal to that of mastectomy even in patients with partial response (PR) (77.4% vs. 64.1%, P = 0.013), no response (NR) (44.9% vs. 64.2%, P = 0.33), or N1 stage (75.7% vs. 57.4%, P = 0.0021). In the N1-PR cohort, mastectomy may lead to worse OS (P = 0.0012). Besides, between reconstruction and BCT, there was no statistical difference in OS or BCSS (P > 0.05). CONCLUSION: Our study reveals the necessity of breast surgical de-escalation. Besides, physicians should actively recommend reconstruction for individuals who strongly desire mastectomy.

Favorable outcome of neoadjuvant endocrine treatment than surgery-first in female HR-positive/HER2-negative breast cancer patients-A NCDB analysis (2010-2016).

PURPOSE: To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients. DATA AND METHODS: We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. RESULTS: Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). CONCLUSION: NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.

Can neoadjuvant systemic therapy provide additional benefits for T1 HER2+ breast cancer patients: a subgroup analysis based on different high-risk signatures.

INTRODUCTION: Neoadjuvant systemic therapy (NAST) is vital in the management of HER2-positive (HER2+) breast cancer. Nevertheless, the indications for NAST in tumors <2 cm remain controversial. METHOD: A total of 7961 patients were screened from the Surveillance, Epidemiology, and End Result database. Independent prognostic factors were identified using multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were used to simulate whether NAST would provide a survival benefit with different high-risk characteristics. Nomograms were constructed, and an internal validation cohort was employed. RESULTS: Of the 7961 included patients, 1137 (14.3%) underwent NAST. In the total population, NAST was associated with poorer overall survival (OS) and breast cancer-specific survival (BCSS) (OS: P = 0.00093; BCSS: P  <  0.0001). Multivariate Cox analysis confirmed that NAST markedly affected the prognosis of enrolled patients. Besides, a direct association between T, N, age, subtype, and prognosis was observed. Subgroup analyses yielded in these three subgroups, T1c, hormone receptor-negative, and 61-69 years of age, NAST and AST had comparable OS, while NAST possessed worse BCSS. Notably, even in the N3, we still did not observe any additional benefit of NAST. The calculated C-index of 0.72 and 0.73 confirmed the predictability of the nomograms. The AUCs exhibit consistency in the training and validation cohorts. CONCLUSION: Our findings suggest that NAST does not provide additional benefit to patients with T1 HER2+ breast cancer, even in the presence of lymph node metastasis, T1c, or hormone receptor negativity. This study facilitates the implementation of individualized management strategies.

The Efficiency and Toxicity Of Anlotinib in Combination With Docetaxel Followed by Epirubicin and Cyclophosphamide Regimen as Neoadjuvant Treatment in IIB to IIIA Triple Negative Breast Cancer: A Single-Arm, Multicenter, Open-Label, Phase II Study.

BACKGROUND: The combination of neoadjuvant chemotherapy and anti-angiogenesis therapy for patients with triple-negative breast cancer (TNBC) remains inadequately supported by evidence. We conducted a single-arm, open-label, multicenter, phase II trial to evaluate the efficacy and toxicity of anlotinib plus epirubicin and cyclophosphamide followed by paclitaxel in patients with IIB to IIIA stage TNBC. METHODS: Newly diagnosed patients received epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m2 (21 days per cycle; total of 4 cycles), along with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total of 4 cycles). Subsequently, patients underwent surgery. The primary endpoint of this study was pathologic complete response (pCR). RESULTS: Among the 34 included patients, the median age was 46.5 years (range: 27-72); all were female. Pathological assessment revealed that 17 patients achieved RCB 0 response, which is currently defined as pathologic complete response; 3 patients achieved RCB 1; 12 patients achieved RCB 2; and 1 patient achieved RCB 3. The probability of a grade 3 adverse reaction was 17.6%, and no grade 4 adverse reactions occurred. The most common hematological adverse reaction was leukopenia (13/34, 38.2%), of which 5.9% (2/34) were grade 3. The most common non-hematological adverse reactions were oral mucositis (16/34, 58.8%), fatigue (50.0%), hand-foot syndrome (50.0%), hypertension (44.1%), bleeding (44.1%), and alopecia (32.4%). CONCLUSION: The combination of anlotinib and EC-T chemotherapy demonstrated tolerable side effects in the neoadjuvant treatment of early TNBC. pCR was higher than what has been reported in previous clinical studies of chemotherapy alone. This study provides additional rationale for using anlotinib plus docetaxel-epirubicin-based chemotherapy regimen in patients with early-stage TNBCs.

"On/off"-switchable crosslinked PTX-nanoformulation with improved precise delivery for NSCLC brain metastases and restrained adverse reaction over nab-PTX.

Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions. In this study, we address these challenges by designing a "on/off" switchable crosslinked paclitaxel (PTX) nanocarrier, BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct "on/off" switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The "off" state of BPM-PD@PTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the "on" state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients.

PIK3CA mutation-driven immune signature as a prognostic marker for evaluating the tumor immune microenvironment and therapeutic response in breast cancer.

PURPOSE: Gene mutations drive tumor immune microenvironment (TIME) heterogeneity, in turn affecting prognosis and immunotherapy efficacy. PIK3CA is the most frequently mutated gene in breast cancer (BC), yet its relevance to BC prognosis remains controversial. Herein, we sought to determine the impact of PIK3CA mutation-driven immune genes (PDIGs) on BC prognosis in relation to TIME heterogeneity. METHODS: PIK3CA mutation characteristics were compared and verified between the TCGA-BRCA dataset and a patient cohort from our hospital. PIK3CA mutation-driven differentially expressed genes were identified for consensus clustering and weighted gene co-expression network analysis to select the modules most relevant to the immune subtype. Thereafter, the two were intersected to obtain PDIGs. Univariate Cox, LASSO, and multivariate Cox regression analyses were sequentially performed on PDIGs to obtain a PIK3CA mutation-driven immune signature (PDIS), which was then validated using the Gene Expression Omnibus (GEO) database. Differences in functional enrichment, mutation landscape, immune infiltration, checkpoint gene expression, and drug response were compared between different risk groups. RESULTS: PIK3CA mutation frequencies in the TCGA and validation cohorts were 34.49% and 40.83%, respectively. PIK3CA mutants were significantly associated with ER, PR, and molecular BC subtypes in our hospital cohort. The PDIS allowed for effective risk stratification and exhibited prognostic power in TCGA and GEO sets. The low-risk patients exhibited greater immune infiltration, higher expression of common immune checkpoint factors, and lower scores for tumor immune dysfunction and exclusion. CONCLUSION: The PDIS can be used as an effective prognostic model for predicting immunotherapy response to guide clinical decision-making.

Construction and Validation of a Nomogram Predicting the Overall Survival Benefit of Unilateral Breast Cancer Patients Undergoing Contralateral Prophylactic Mastectomy.

BACKGROUND: Currently, research on the prognostic factors of unilateral breast cancer (UBC) patients receiving contralateral prophylactic mastectomy (CPM) is limited. This study aimed to construct a new nomogram to predict these patients' overall survival (OS). METHODS: In this retrospective study, 88,477 patients who underwent CPM or unilateral mastectomy (UM) were selected from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analyses were used to determine the difference in the impact of the 2 surgical methods on the prognosis. Multivariate Cox analysis was used to determine the best prognostic variable and construct a nomogram. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the discrimination capability and clinical effectiveness of the nomogram. RESULTS: The prognosis of patients receiving CPM and UM was significantly different. The DCA curves indicated that the nomogram could provide more excellent clinical net benefits for these patients. The NRI and IDI of the nomogram demonstrated that its performance was better than that of the classical tumor-node-metastasis (TNM) staging system. CONCLUSION: This study developed and validated a practical nomogram to predict the OS of UBC patients undergoing CPM, which provided a beneficial tool for clinical decision-making management.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Effect of T Stages on the Choice of Axillary Evaluation Modality in Breast Cancer Patients With 1-2 Sentinel Lymph Node Metastases.

INTRODUCTION: The survival benefit of axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB) combined with radiation, and ALND combined with radiation remains unclear in breast cancer (BC) patients with 1-2 metastatic sentinel lymph nodes (SLNs). This study aims to rigorously evaluate the prognostic impact of these axillary evaluation modalities on BC patients with varying T-stages and to construct a survival prediction nomogram. METHODS: Following screening for inclusion and exclusion criteria, data pertaining to BC patients were extracted from the SEER database. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Kaplan-Meier curves and Cox proportional hazards model among patients with different stages who underwent various axillary evaluation modalities. A nomogram was constructed to predict the probability of OS and BCSS. RESULTS: A total of 20,283 patients were included, comprising 9626 who underwent breast-conserving surgery (BCS) and 10,657 who underwent mastectomy. In the T4 stage stratified analysis, both BCS and mastectomy groups exhibited superior OS and BCSS with ALND compared to SLNB combined with radiation. Further, ALND combined with radiation improved OS. However, for T1-3 stages, patients treated with ALND experienced similar or worse survival compared to those treated with SLNB combined with radiation. The calibration curve and C-index (0.746-0.794) of the nomogram demonstrated the efficacy of the survival prediction model. CONCLUSION: In T1-3 BC patients with 1-2 metastatic SLNs, SLNB combined with radiation is a safe alternative to ALND. Conversely, for T4 patients, ALND combined with radiation may offer a preferable choice.

New progress in the deep understanding of the biocake layer property: Combined effect of neglected protein secondary structure, morphology, and mechanism.

The application of magnetic fields (MFs) and magnetic particles (MPs) in water treatment has attracted widespread attention due to their stability, strong biological compatibility, and less chemical consumption. This study introduced MPs and MFs to GDM and probed their effects on filtration performance. Predeposited large MPs (P-large) and batch-added little MPs (B-little) intervened biocake layer development, forming more open and porous structures, they also reduced biomass secretion, resulting in flux increases of 13 % in P-large and 40 % in B-little than P-little, respectively. Besides, MFs controlled MPs distribution on the biocake layer, resulting in forming of more rough and open structures. A relatively lower magnetic field of 20 mT facilitated biomass secretion, while a higher magnetic field of 50 mT decreased biomass. Furthermore, applying magnetic fields decreased the ratios of α-helix and ß-sheet, and increased random coil percentage. Thus, applying magnetic field mediation would contribute to the flux improvements in I-20 and I-50 by 29 % and 32 % relative to I-0. Economic analysis suggested introducing MPs and MFs to GDM was economically feasible, synergy of MPs and MFs had more economic advantages on the community scale and MPs-assisted GDM had significant economic advantages on both community and household scales. Future works should focus on developing new technologies for the recycling of MPs and membranes. This study provided new insight into the protein secondary structures associated with GDM performance and would encourage new sustainable MFs and MPs-assisted GDM technological developments.

Breast cancer is associated with coronary heart disease: a cross-sectional survey of NHANES 1999-2018.

Background: Understanding the correlation between female breast cancer (BC) and the prevalence of coronary heart disease (CHD) is important for developing prevention strategies and reducing the burden of female social disease. This study aimed to evaluate the relationship between BC and CHD using data from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018. Methods: The study cohort included 16,149 eligible non-pregnant female participants aged 20 years or older. Logistic regression was used to analyze the relationship between BC and CHD, excluding the interaction between covariates and BC through hierarchical subgroup analysis. Results: The study found that participants with BC had a 2.30 times greater risk of developing CHD compared to those without BC [95% confidence interval (CI): 2.29-2.31]. After adjusting for all included covariates, BC was still significantly associated with CHD risk (odds ratio: 1.11, 95% CI: 1.10-1.12). When participants were stratified by age, education level, and prevalence of hypertension, it was evident that participants with BC had a higher risk of developing CHD compared to those without BC, although the effect of BC on CHD varied across stratification. Conclusions: Our study demonstrates the close relationship between CHD and female BC. Therefore, it is necessary to screen patients with CHD for BC and monitor BC survivors for the long-term risk of developing CHD.

Artificial intelligence system-based histogram analysis of computed tomography features to predict tumor invasiveness of ground-glass nodules.

Background: The use of an artificial intelligence (AI)-based diagnostic system can significantly aid in analyzing the histogram of pulmonary nodules. The aim of our study was to evaluate the value of computed tomography (CT) histogram indicators analyzed by AI in predicting the tumor invasiveness of ground-glass nodules (GGNs) and to determine the added value of contrast-enhanced CT (CECT) compared with nonenhanced CT (NECT) in this prediction. Methods: This study enrolled patients with persistent GGNs who underwent preoperative NECT and CECT scanning. AI-based histogram analysis was performed for pathologically confirmed GGNs, which was followed by screening invasiveness-related factors via univariable analysis. Multivariable logistic models were developed based on candidate CT histogram indicators measured on either NECT or CECT. Receiver operating characteristic (ROC) curve and precision-recall (PR) curve were used to evaluate the models' performance. Results: A total of 116 patients comprising 121 GGNs were included and divided into the precancerous lesion and adenocarcinoma groups based on invasiveness. In the AI-based histogram analysis, the mean CT value [NECT: odds ratio (OR) =1.009; 95% confidence interval (CI): 1.004-1.013; P<0.001] and solid component volume (NECT: OR =1.005; 95% CI: 1.000-1.010; P=0.032) were associated with the adenocarcinoma and used for multivariable logistic modeling. The area under ROC curve (AUC) and PR curve (AUPR) were not significantly different between the NECT model (AUC =0.765, 95% CI: 0.679-0.837; AUPR =0.907, 95% CI: 0.825-0.953) and the optimal CECT model (delayed phase: AUC =0.772, 95% CI: 0.687-0.843; AUPR =0.895, 95% CI: 0.812-0.944). No significantly different metrics were observed between the NECT and CECT models (precision: 0.707 vs. 0.742; P=0.616). Conclusions: The AI diagnostic system can help in the diagnosis of GGNs. The system displayed decent performance in GGN detection and alert to malignancy. Mean CT value and solid component volume were independent predictors of tumor invasiveness. CECT provided no additional improvement in diagnostic performance as compared with NECT.

Prognostic value and mode selection of locoregional treatment in Stage-IV breast cancer patients.

PURPOSE: This study aimed to assess the actual prognostic significance of different locoregional treatment (LRT) (surgery and radiotherapy) modalities for stage-IV  breast cancer (BC) patients and construct a competing risk nomogram to make precise predictions of the breast cancer-specific death (BCSD) risk among LRT recipients. METHODS: A total of 9279 eligible stage-IV BC patients from the Surveillance Epidemiology and End Results (SEER) database were included in this study. Initially, we evaluated the impact of LRT on survival both before and after the propensity score matching (PSM). Then, we used the Cox hazard proportional model and competing risk model to identify the independent prognostic factors for LRT recipients. Based on the screened variables, a comprehensive nomogram was established. RESULTS: Kaplan-Meier curves demonstrated that LRT significantly prolonged overall survival (OS) and breast cancer-specific survival (BCSS) (P < 0.001). In addition, patients treated with surgery combined with postoperative radiotherapy (PORT) possessed the optimal survival (P < 0.001). Regardless of the surgical modalities, primary tumor resection combined with radiotherapy could ameliorate the prognosis (P < 0.05). Subgroup analysis showed that in patients with T2-T4 stage, PORT had a survival benefit compared with those undergoing surgery combined with preoperative radiotherapy (PRRT) and surgery only. Based on the screened independent prognostic factors, we established a comprehensive nomogram to forecast BCSD in 1 year, 2 years and 3 years, which showed robust predictive ability. CONCLUSION: PORT was associated with a lower BCSD in stage-IV BC patients. The practical nomogram could provide a precise prediction of BCSD for LRT recipients, which was meaningful for patients' individualized management.

Gravity-driven membrane system treating heavy metals-containing secondary effluent: Improved removal of heavy metals and mechanism.

This study aimed at investigating the removal performance of the gravity-driven membrane (GDM) system in treating the heavy metals-containing secondary effluent, as well as evaluating the respective roles of Fe and Mn addition on the removal of heavy metals. GDM process with the formation of biocake layer exerted effective removals of Cr, Pb and Cd, with an average removal efficiency of 98%, 95% and 40%, respectively, however, after removing the biocake layer, the removal efficiencies of Cr, Pb and Cd reduced to 59%, 85% and 19%, respectively, indicating that the biocake layer played a fundamental role in removing heavy metals. With the assistance of Fe, the removal efficiency of heavy metals increased, and exhibited a positive response to the Fe dosage, due to the adsorption by the freshly generated iron oxides. On the contrary, the Mn involvement would result in the reduction of Cd removal due to the competitive adsorption of residual dissolved Mn2+ and Cd. Furthermore, the addition of a high dosage of Fe increased the diversity of eukaryotic communities and facilitated the elimination of heavy metals, however, the involvement of Mn would lead to a reduction in microbial diversity, resulting in a decrease of heavy metal removal efficiency. These findings are expected to develop new tactics to enhance heavy metal removal and promote widespread application of GDM technology in the fields of deep treatment of heavy metals-containing wastewater and reclamation of secondary effluent.

What impacts ecosystem services in tropical coastal tourism cities? A comparative case study of Haikou and Sanya, China.

The ecological environment of tourism-oriented towns is attracting increasing attention. Taking the cities of Haikou and Sanya as examples, we examined changes in six ecosystem services (ES), including water conservation (WC), crop production (CP), soil retention (SR), carbon storage (CS), habitat quality (HQ), and tourism recreation (TR) from 2005 to 2020. From the three perspectives of geographical environment, socioeconomic development, and tourism development force, 14 indicators were chosen to examine the impact on ES. Except for Haikou's TR, the other ES of Haikou and Sanya showed a decreasing trend from 2005 to 2020. The values of six ES were lower in coastal zones than in noncoastal zones, which were more obvious in Sanya. Specifically, the areas of low value in Sanya were concentrated in the coastal region, and the areas with low value in Haikou were primarily distributed in blocks along the coast and in bands or points in the central and southern areas. From the perspective of influencing factors, the natural environmental factors dominate in Haikou, followed by the socio-economic factors and finally the tourism development factors, while the natural environmental factors also dominate in Sanya, followed by the tourism development factors and finally the socio-economic factors. We provided recommendations for sustainable tourism development in Haikou and Sanya. This study has significant implications for both integrated management and scientific decision-making to enhance the ES of tourism destinations.

Comprehensive analysis of nicotinamide metabolism-related signature for predicting prognosis and immunotherapy response in breast cancer.

Background: Breast cancer (BC) is the most common malignancy among women. Nicotinamide (NAM) metabolism regulates the development of multiple tumors. Herein, we sought to develop a NAM metabolism-related signature (NMRS) to make predictions of survival, tumor microenvironment (TME) and treatment efficacy in BC patients. Methods: Transcriptional profiles and clinical data from The Cancer Genome Atlas (TCGA) were analyzed. NAM metabolism-related genes (NMRGs) were retrieved from the Molecular Signatures Database. Consensus clustering was performed on the NMRGs and the differentially expressed genes between different clusters were identified. Univariate Cox, Lasso, and multivariate Cox regression analyses were sequentially conducted to develop the NAM metabolism-related signature (NMRS), which was then validated in the International Cancer Genome Consortium (ICGC) database and Gene Expression Omnibus (GEO) single-cell RNA-seq data. Further studies, such as gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, SubMap, and Immunophenoscore (IPS) algorithm, cancer-immunity cycle (CIC), tumor mutation burden (TMB), and drug sensitivity were performed to assess the TME and treatment response. Results: We identified a 6-gene NMRS that was significantly associated with BC prognosis as an independent indicator. We performed risk stratification according to the NMRS and the low-risk group showed preferable clinical outcomes (P < 0.001). A comprehensive nomogram was developed and showed excellent predictive value for prognosis. GSEA demonstrated that the low-risk group was predominantly enriched in immune-associated pathways, whereas the high-risk group was enriched in cancer-related pathways. The ESTIMATE and CIBERSORT algorithms revealed that the low-risk group had a higher abundance of anti-tumor immunocyte infiltration (P < 0.05). Results of Submap, IPS, CIC, TMB, and external immunotherapy cohort (iMvigor210) analyses showed that the low-risk group were indicative of better immunotherapy response (P < 0.05). Conclusions: The novel signature offers a promising way to evaluate the prognosis and treatment efficacy in BC patients, which may facilitate clinical practice and management.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.