RESUMEN
Primary aldosteronism (PA) is a common cause of secondary hypertension. Adrenalectomy is an effective treatment for unilateral PA, particularly aldosterone-producing adenoma (APA), resulting in improvements in biochemical parameters and blood pressure in the vast majority of patients. The article provides a comprehensive overview of PA, focusing on the outcomes of adrenalectomy for PA and the factors that may suggest prognostic implications. Analysis of the outcome of different PA patients undergoing adrenalectomy in terms of preoperative factors, vascular and adipose conditions, type of pathology, and somatic variants. In addition, it is recommended to use the histopathology of primary aldosteronism (HISTALDO) consensus to classify the patient's pathological type, with classical and nonclassical pathological types showing a different prognosis and possibly being associated with an unresected contralateral adrenal gland. The primary aldosteronism surgical outcome (PASO) consensus sets uniform standards for postoperative outcomes in unilateral PA, but its setting of thresholds remains controversial. Partial adrenalectomy shows similar surgical results and fewer postoperative complications than total adrenalectomy, but there is a risk of missing the true source of abnormal aldosterone secretion. Steroid profiling and functional imaging techniques offer alternative options to adrenal vein sampling (AVS) for unilateral and bilateral judgments in patients with PA. A combination of factors is needed to predict the prognosis of PA patients undergoing adrenalectomy in order to manage patient expectations of the outcome of the procedure and to closely monitor blood pressure and biochemical parameters in patients who suggest a poorer prognosis.
Asunto(s)
Adrenalectomía , Hiperaldosteronismo , Hiperaldosteronismo/cirugía , Humanos , Pronóstico , Resultado del Tratamiento , Aldosterona/sangre , Aldosterona/metabolismo , Hipertensión/cirugía , Hipertensión/etiologíaRESUMEN
BACKGROUND: Bladder cancer (BLCA) is one of the top ten most common cancers in the world. Aberrant sialylation is a common feature in tumorigenesis and tumor immunity. This study seeks to explore the potential impact of sialyltransferase ST3Gal5 on BLCA. METHODS: Initially, glycosyltransferase-related DEGs (GRDEGs) were identified using multiple bioinformatics approaches in TCGA-BLCA cohort and validated using GEO databases. Clinical prognosis integration facilitated the determination of ST3Gal5 as an independent prognostic factor in BLCA, employing univariate and multivariate Cox regression analyses. Immune cell infiltration was assessed via CIBERSORT and ssGSEA analyses, while HLA and immune checkpoint genes' levels, along with drug sensitivity, were evaluated in low- and high-ST3Gal5 groups. The TIDE and IPS scores were used to gauge the immune checkpoint blockade (ICB) response. Furthermore, functional experiments, both in vivo and in vitro, were conducted to elucidate the biological roles of ST3Gal5. RESULTS: In agreement with bioinformatics findings, ST3Gal5 expression was down-regulated in BLCA tissues and cells, correlating with poorer prognostic outcomes. The StromalScore, ImmuneScore, and ESTIMATEScore were significantly elevated in low-ST3Gal5 group. Moreover, the levels of HLA and immune checkpoint genes were upregulated in low-ST3Gal5 group. Down-regulated ST3Gal5 promoted the proliferation, migration, and invasion of BLCA cells in vivo and in vitro. CONCLUSION: Our findings demonstrated that low ST3Gal5 level promoted tumorigenesis and progression of BLCA, implying its potential as a predictive biomarker and therapeutic target.
Asunto(s)
Biología Computacional , Regulación Neoplásica de la Expresión Génica , Sialiltransferasas , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/mortalidad , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Humanos , Biología Computacional/métodos , Animales , Línea Celular Tumoral , Pronóstico , Proliferación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , beta-Galactosida alfa-2,3-Sialiltransferasa , Ratones , Masculino , Femenino , Movimiento Celular , Ratones DesnudosRESUMEN
Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune senescence particularly T cell function, which can limit the effectivity of cancer immunotherapies. Furthermore, age-related immune dysregulation increases the exhaustion of immune cells, characterized by the dysregulation of ICI-related biomarkers and a dampened response to ICI. Our review aims to provide a comprehensive understanding of the mechanisms that contribute to the impact of age on ICI-related biomarkers and ICI response. Understanding these mechanisms will facilitate the development of treatment approaches tailored to elderly individuals with cancer.
Asunto(s)
Investigación Biomédica , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias , Anciano , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Envejecimiento , Neoplasias/tratamiento farmacológicoRESUMEN
Hot air (HA) drying caused quality damage of grains with long treatment time. Radio frequency (RF) heating as an emerging technology was applied to improve drying quality of cereals effectively. The effects of HA-RF drying (50 °C, 70 °C, 90 °C) of corn kernels on the morphology, structure, and physicochemical properties of starch were investigated and compared with HA drying. The surface of treated starch became rough, along with fragments and pores. Drying treatments increased the amylose content from 10.59 % to 23.88 % and the residual protein content of starch from 0.58 % to 1.23 %, and reduced the crystallinity from 31.95 % to 17.15 % and short-range order structures of starch from 0.918 to 0.868. The change of structures in turn resulted in the increase of pasting viscosity, gelatinization temperature, storage modulus and loss modulus. Furthermore, the HA-RF dried starch displayed stronger thermal stability, higher gelatinization degree and better gelation properties than the HA-treated starch at the same temperature. The data proved that the synergistic effects of HA and RF were more effective in modulating the starch structure and improving the functional characteristics of corn starch. This paper would like to provide potential reference for better application of HA-RF technologies to corn.
Asunto(s)
Calor , Almidón , Zea mays , Zea mays/química , Almidón/química , Amilosa/química , Ondas de Radio , Viscosidad , Desecación/métodos , AireRESUMEN
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the agarose gel electrophoretic bands shown in Fig. 4A for PKC were strikingly similar to bands that had already appeared in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 165172, 2016; DOI: 10.3892/or.2016.4794].
RESUMEN
BACKGROUND: CD56 has been observed in malignant tumours exhibiting neuronal or neuroendocrine differentiation, such as breast cancer, small-cell lung cancer, and neuroblastoma. Abnormal glycosylation modifications are thought to play a role in regulating tumour cell proliferation, migration, and invasion. Nevertheless, the exact roles and molecular mechanisms of CD56 and polysialylated CD56 (PSA-CD56) in the development and progression of clear cell renal cell carcinoma (ccRCC) remain elusive. Here we unveil the biological significance of CD56 and PSA-CD56 in ccRCC. METHODS: In this study, we employed various techniques, including immunohistochemistry (IHC), RT-qPCR, and western blot, to examine the mRNA and protein expression levels in both human ccRCC tissue and cell lines. Lentivirus infection and CRISPR/Cas9 system were utilized to generate overexpression and knockout cell lines of CD56. Additionally, we conducted several functional assays, such as CCK-8, colony formation, cell scratch, and transwell assays to evaluate cell growth, proliferation, migration, and invasion. Furthermore, we established a xenograft tumor model to investigate the role of CD56 in ccRCC in vivo. To gain further insights into the molecular mechanisms associated with CD56, we employed the Hedgehog inhibitor JK184 and the ß-catenin inhibitor Prodigiosin. RESULTS: CD56 was significantly overexpressed in both human ccRCC tissues and renal cancer cell lines compared to adjacent normal tissues and normal renal epithelial cells. In vitro and in vivo experiments revealed that the knockout of CD56 inhibited the proliferation, migration, and invasion capabilities of ccRCC cells, whereas the overexpression of PSA-CD56 promoted these capacities. Finally, PSA-CD56 overexpression was found to activate both the Hedgehog and Wnt/ß-catenin signaling pathways. CONCLUSION: Our findings demonstrate that the oncogenic function of CD56 polysialylation plays a vital role in the tumorigenesis and progression of ccRCC, implying that targeting PSA-CD56 might be a feasible treatment target for ccRCC.
RESUMEN
Whether economic openness (EO) is conducive to promoting economic growth has become a common concern of many scholars and policymakers in China. Based on the panel sample data of 30 provinces in China from 2004 to 2018, this paper adopts an empirical model to test the relationship between EO and regional economic growth. The study identifies that expanding EO increases regional economic growth. After dealing with endogeneity issues, the results remain robust. The results of the mediation effect model show that technological innovation is an important channel for EO to accelerate economic growth. With the improvement of regional economic development, the benefits of EO will increase. However, its positive effect has slowed down in regions with very high levels of economic development. The outbreak of the financial crisis has weakened the driving force of EO on economic growth, while the Belt and Road Initiative has strengthened the positive impact of EO. In addition, when introducing the threshold variable of policy support to examine the nonlinear relationship between variables, it is found that deepening the policy intensity will significantly improve economic growth due to the benefits of EO.
RESUMEN
Background: It is anticipated that there will be a large rise in the number of tumor diagnoses and mortality in those aged 65 and older over the course of upcoming decades. Immune checkpoint inhibitors, often known as ICIs, boost immune system activity by selectively targeting ICI genes. On the other hand, old age may be connected with unfavorable results. Methods: The Cancer Genome Atlas (TCGA) provided gene expression data from ccRCC tissue and key clinical variables. ICI gene databases were applied and verified using the GEO database. Results: We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival. Then, by utilizing a new nomogram method, the TNFSF15 gene and age predicting values were estimated at one, three, and five years (85%, 81%, and 81%), respectively, and our age-related risk score was significant even after multivariable analysis (HR = 1.518, p = 0.009, CI = 1.1102.076). TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001). A negative connection between age and the TNFSF15 gene expression was discovered by correlation analysis (p = 0.0001). The verification of the gene by utilizing GEO (GSE167093) with 604 patients was obtained as external validation that showed significant differences in the TNFSF15 gene between young and elderly patients (p = 0.007). Additionally, the protein-protein interactions of the TNFSF15 gene with other ICI genes and aging-related genes was determined. In addition, the TNFSF15 expression was significantly correlated with pathological stages (p = 0.018). Furthermore, it was discovered that the biological processes of senescence, cellular senescence, the immune system, and many immune cell infiltration and immune function types are all closely tied. Conclusions: Along with the risk score evaluation, the ICI gene TNFSF15 was identified as a tumor suppressor gene related to inequalities in age survival and is associated with pathological stages and different immunity statuses. The aging responses of ccRCC patients and related gene expression need further investigation in order to identify potential therapeutic targets.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Anciano , Humanos , Carcinoma de Células Renales/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/patología , Genómica , Envejecimiento/genética , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis TumoralRESUMEN
Fresh pork is prone to spoilage during storage, transportation, and sale, resulting in reduced freshness. The total viable count (TVC) and total volatile basic nitrogen (TVB-N) content are key indicators for evaluating the freshness of fresh pork, and when they reach unacceptable limits, this seriously threatens dietary safety. To realize the on-site, low-cost, rapid, and non-destructive testing and evaluation of fresh pork freshness, a miniaturized detector was developed based on a cost-effective multi-channel spectral sensor. The partial least squares discriminant analysis (PLS-DA) model was used to distinguish fresh meat from deteriorated meat. The detector consists of microcontroller, light source, multi-channel spectral sensor, heat-dissipation modules, display system, and battery. In this study, the multispectral data of pork samples with different freshness levels were collected by the developed detector, and its ability to distinguish pork freshness was based on different spectral shape features (SSF) (spectral ratio (SR), spectral difference (SD), and normalized spectral intensity difference (NSID)) were compared. The experimental results show that compared with the original multispectral modeling, the performance of the model based on spectral shape features is significantly improved. The model established by optimizing the spectral shape feature variables has the best performance, and the discrimination accuracy of its prediction set is 91.67%. In addition, the validation accuracy of the optimal model was 86.67%, and its sensitivity and variability were 87.50% and 85.71%, respectively. The results show that the detector developed in this study is cost-effective, compact in its structure, stable in its performance, and suitable for the on-site digital rapid non-destructive testing of freshness during the storage, transportation, and sale of fresh pork.
Asunto(s)
Carne de Cerdo , Carne Roja , Animales , Porcinos , Carne Roja/análisis , Análisis de los Mínimos Cuadrados , Carne , Nitrógeno/análisisRESUMEN
Background: To construct and validate a deep learning cluster from whole slide images (WSI) for depicting the immunophenotypes and functional heterogeneity of the tumor microenvironment (TME) in patients with bladder cancer (BLCA) and to explore an artificial intelligence (AI) score to explore the underlying biological pathways in the developed WSI cluster. Methods: In this study, the WSI cluster was constructed based on a deep learning procedure. Further rerecognition of TME features in pathological images was applied based on a neural network. Then, we integrated the TCGA cohort and several external testing cohorts to explore and validate this novel WSI cluster and a corresponding quantitative indicator, the AI score. Finally, correlations between the AI cluster (AI score) and classical BLCA molecular subtypes, immunophenotypes, functional heterogeneity, and potential therapeutic method in BLCA were assessed. Results: The WSI cluster was identified associated with clinical survival (P < 0.001) and was proved as an independent predictor (P = 0.031), which could also predict the immunology and the clinical significance of BLCA. Rerecognition of pathological images established a robust 3-year survival prediction model (with an average classification accuracy of 86%, AUC of 0.95) for BLCA patients combining TME features and clinical features. In addition, an AI score was constructed to quantify the underlying logic of the WSI cluster (AUC = 0.838). Finally, we hypothesized that high AI score shapes an immune-hot TME in BLCA. Thus, treatment options including immune checkpoint blockade (ICB), chemotherapy, and ERBB therapy can be used for the treatment of BLCA patients in WSI cluster1 (high AI score subtype). Conclusions: In general, we showed that deep learning can predict prognosis and may aid in the precision medicine for BLCA directly from H&E histology, which is more economical and efficient.
RESUMEN
Background: Neurofibromatosis type 1, also known as NF1, is a disorder that is passed down in an autosomal dominant manner. It manifests in a wide variety of tumors and affects several organ systems. It is expected that those carrying the NF1 gene will develop a rare mesenchymal tumor known as a gastrointestinal stromal tumor (GIST) more than general population. Case report: This research discusses a 42-year-old female patient with NF1 who was identified with a duodenal GIST but clinically and radiographically misinterpreted as having a retroperitoneal neurofibroma. She had minimally invasive retroperitoneal laparoscopic surgery to remove the tumor and primary anastomosis of the affected duodenal wall. A spindle cell GIST was entirely excised during surgery, as indicated by the pathologist. As a consequence of dialogue at a multidisciplinary team meeting, the patient was discharged from the hospital on the fourth postoperative day and is presently undergoing regular clinical follow-up. Conclusion: Anatomically problematic sites, such as the duodenal GIST in NF1 patients, can be treated safely with the laparoscopic retroperitoneal approach even when retroperitoneal neoplasia arises from the intrabdominal structure and protrudes into the retroperitoneal region.
RESUMEN
Numerous rare urinary tract (UT) cancers lack adequate understanding of survival and therapeutic options, and nearly all responses to systemic therapy are unsatisfactory, yet clinical research is scarce. METHODS: Between 2010 and 2015, a total of (14,622 patients) with uncommon UT cancer (62.5%) in the overall survival (OS) group and (37.5%) in the cancer specific survival (CSS)group were identified in the SEER database. multimodality therapeutic approach on OS and CSS were compared. RESULTS: In uncommon UT malignancies, OS outperformed CSS in the locoregional stage (P < 0.05), but not in the distant stage (P = 0.34). Non-performed surgery had poor survival in both OS (HR 1.647; 95% CI (1.461-1.856)) and CSS (HR 1.573; 95% CI (1.399-1.769)) respectively (P < 0.05). There were no significant differences in survival in the CSS group between those who received or did not obtain chemotherapy. CONCLUSIONS: The OS group survives substantially longer than the CSS group in the locoregional stage, but not at the distant stage. While both the OS and CSS groups of the locoregional stage were linked with improved survival after surgery, chemotherapy treatment decreased OS but not CSS in patients with uncommon urological cancers. There were no differences in radiation between the OS and CSS.
Asunto(s)
Neoplasias Urológicas , Humanos , Estadificación de Neoplasias , Programa de VERF , Neoplasias Urológicas/cirugíaRESUMEN
Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system, accounting for around 2% of all cancer diagnoses and deaths worldwide. Clear cell RCC (ccRCC) is the most prevalent and aggressive histology with an unfavorable prognosis and inadequate treatment. Patients' progression-free survival is considerably improved by surgery; however, 30% of patients develop metastases following surgery. Identifying novel targets and molecular markers for RCC prognostic detection is crucial for more accurate clinical diagnosis and therapy. Glycosylation is a critical post-translational modification (PMT) for cancer cell growth, migration, and invasion, involving the transfer of glycosyl moieties to specific amino acid residues in proteins to form glycosidic bonds through the activity of glycosyltransferases. Most cancers, including RCC, undergo glycosylation changes such as branching, sialylation, and fucosylation. In this review, we discuss the latest findings on the significance of aberrant glycans in the initiation, development, and progression of RCC. The potential biomarkers of altered glycans for the diagnosis and their implications in RCC have been further highlighted.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/metabolismo , Glicosilación , Glicosiltransferasas/metabolismo , Humanos , Neoplasias Renales/patología , PolisacáridosRESUMEN
In the past 40 years, the continuous strengthening of the greenhouse effect has led to a significant increase in the global average temperature. Although people's understanding of climate change has been strengthened, the world has not yet witnessed a significant decline in pollutant emissions; hence it is imperative to get to the root cause. This paper is based on the STIRPAT model framework and uses the panel data of G20 countries over the period 1999-2019 to examine the role of financial development on carbon emissions under good governance. The results show that financial development significantly promotes carbon dioxide emissions, and the impact presents an inverted "U"-shaped trend when the quadratic term of financial development is introduced. Surprisingly, governance quality indicators increase carbon emissions. However, financial development accompanied by good governance suppresses carbon emissions. Moreover, according to the grouped results of developed and developing countries, different nations should adopt differentiated strategies in development finance to implement the carbon emission targets proposed by the G20. In addition, this paper also confirms the existence of the Environmental Kuznets Curve hypothesis. In light of this, policymakers should optimize the quality of governance while shifting their agendas toward environmentally responsible financial practices to promote financial development to improve environmental quality effectively. Furthermore, strengthen international cooperation, enhance public environmental protection concepts, and take joint actions to achieve low-carbon and win-win results.
Asunto(s)
Dióxido de Carbono , Desarrollo Económico , Cambio Climático , Efecto Invernadero , Humanos , Cooperación InternacionalRESUMEN
Chronic primary pelvic pain syndrome (CPPPS) is a heterogeneous disease with unknown pathogenesis and a lack of distinct pathological features, which complicates diagnosis and therapy and has a significant impact on patients' daily life. Because pharmacological management is ineffective and long-term use may result in additional system damage, developing a more effective treatment is critical. Neuromodulation has advanced rapidly over the last few decades, and various types of neuromodulations have demonstrated efficacy in the treatment of CPPPS. In this article we discuss the evolution of neuromodulation technology in the treatment of chronic pelvic pain, its application to various subtypes of chronic pelvic pain, and the comparison of relevant efficacy and parameter differences, as well as assess the relative advantages and disadvantages of sacral neuromodulation, percutaneous tibial nerve stimulation , transcutaneous electrical nerve stimulation, electroacupuncture, and pudendal neuromodulation. Furthermore, it was noted that chronic pelvic pain should be evaluated in terms of pain, associated symptoms, psychological problems, and quality of life. Although neuromodulation approaches have been shown to be effective in treating chronic pelvic pain, more extensive multicenter trials are required to confirm this.
RESUMEN
This study aimed to develop a cost-effective fluorescence imaging system to rapidly monitor pork freshness indicators during chilled storage. The system acquired fluorescence images of pork and the color features were extracted from these images to establish partial least squares regression (PLSR) models to predict total volatile basic nitrogen (TVB-N), total viable count (TVC), pH for pork. For TVB-N, TVC and pH values, Rp were 0.92, 0.88 and 0.74, residual predictive deviation (RPD) were 2.24, 2.03, and 1.19, respectively. For TVB-N and TVC indicators showed that the predictive ability of this model was largely comparable to that of fluorescence hyperspectral imaging. However, combining fluorescence and color imaging improved the model's predictive ability. For TVB-N, TVC and pH, Rp were 0.94, 0.93 and 0.85, RPD were 2.62, 2.59, and 1.95, respectively. Therefore, this study developed a system with great potential for detecting the value of most pork quality indicators in real-time.
Asunto(s)
Carne de Cerdo , Carne Roja , Animales , Análisis de los Mínimos Cuadrados , Nitrógeno , Imagen Óptica , Carne Roja/análisis , PorcinosRESUMEN
Deeply investigating the relationship between governance, financial development, and outward foreign direct investment (OFDI) is beneficial to formulating effective policies to accelerate Chinese firms' pace of overseas expansion. Based on the theoretical mechanism analysis, this paper empirically analyzes the impact of Asian governance and financial development on China's OFDI using the panel data of 37 Asian countries from 2003 to 2017. The results show that the host country governance has a negative and statistically significant impact on China's direct investment in Asia. The conclusion remains valid even after overcoming the interference of endogenous and economic cycle fluctuations. Moreover, using the mediating effect model, we find that financial development is an important channel through which host country governance affects China's OFDI. In further discussion, the findings suggest that with the scale of OFDI expanding, the role of governance takes an inverted "U" shape, and the "Belt and Road" initiative (BRI) weakens the negative impact of governance quality on China's OFDI. Furthermore, governance has shown more remarkable restraint on China's OFDI in neighboring, coastal, and low-income countries in the heterogeneity test. âFrom the perspective of host country governance, this paper provides more specific guidance to formulate China's direct investment policy in Asia.
Asunto(s)
Internacionalidad , Inversiones en Salud , Asia , China , Desarrollo Económico , PolíticasRESUMEN
Purpose of the Review. Posterior tibial nerve stimulation (PTNS) techniques have dramatically grown after approval to manage overactive bladder (OAB). The present review will focus on the most current data on PTNS types (percutaneous, transcutaneous, and implant) and their mechanism of action, safety, efficacy, advantages, drawbacks, limitation, and clinical applications. Recent Findings. The present review described the recent studies that addressed the tibial nerve stimulation role in OAB management. BlueWind RENOVA system, Bioness StimRouter, and eCoin are examples of emerging technologies that have evolved from interval sessions (percutaneous PTNS and transcutaneous PTNS) to continuous stimulation (implants). These can be efficiently managed at home by patients with minimum burden on the health system and fewer visits, especially in the COVID-19 pandemic. Summary. Our review shows that the tibial nerve stimulation advancements in OAB treatment have been rapidly increasing over the recent years. It is minimally invasive and effective, similar to sacral nerve stimulation (SNM), but less aggressive. Implantable PTNS has been promised in terms of efficacy, safety, and high acceptance rate. However, evidence is still limited to short-term trials, and tolerability, method, and drawbacks remain challenges.
RESUMEN
BACKGROUND: Tumor-stroma ratio (TSR) and tumor budding (TB) play important roles in muscle-invasive bladder cancer (MIBC). We developed a rating system (TSR-TB type) based on the morphological evaluation of TSR and TB for predicting patient outcome and using individualized care. METHODS: TSR and TB were assessed in publicly accessible MIBC tumor slides from the TCGA database. MIBC patients were classified as low stromal or high stromal type based on TSR, and high stromal type was further classified as compartmentalized or mixed stromal type based on TB. RESULTS: TSR-TB type was an independent adverse prognostic factor for OS (P < 0.001). Low stromal type had a greater prognosis (P < 0.001) and were enriched for FGFR3 mutations (P = 0.001). The mixed stromal type was distinguished by increased M2 macrophage penetration (P < 0.001), anti-tumor immune activity, DNA repair pathway mutations, and poor survival. GSEA showed that certain cancer-related pathways, such as mitotic spindle, PI3K-AKT-MTOR signalingwere hyperactivated in high stromal type (all FDR<0.05). Furthermore, mixed stromal type demonstrated enhanced activation of epithelial mesenchymal transformation (EMT), inflammatory response (all FDR<0.05). CONCLUSION: TSR and TB-based MIBC classification coincides with patient survival and molecular alterations. The identified subtypes may have important implications for individualized MIBC therapy.