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PURPOSE: To assess the predictive role of pretreatment ki67 and Ki67 changes in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC) in various molecular subtypes. METHODS: 1010 BC patients who had undergone anthracycline and taxane-based NAC from January 2012 to July 2017 were retrospectively analyzed. Clinical and pathological parameters of the patients were retrieved and the predictive factors for NAC response were evaluated. RESULTS: 705 patients showed clinical response (cRes), and 131 patients acquired pathologic complete response (pCR). Patients with higher pretreatment Ki67 (≥ 14%), tumor size ≥ 4 cm, and positive clinical nodal had better clinical therapy response, while patients with negative ER and PR, higher pretreatment Ki67 (≥ 14%), and tumor size < 4 cm were more probable to attain pCR. The pretreatment Ki67 could be used as a predictor of NAC only in luminal subtypes, and 25.5% were identified as an ideal cut-off point to differentiate the cRes from non-cRes cases. Although a decrease in Ki67 had been found in almost all molecular subtypes after NAC, no statistically significant differences were found in the decrease of Ki67 were validated between the cRes and non-cRes group in HER2-rich and triple-negative subtypes (P = 0.488 and P = 0.111, respectively). CONCLUSIONS: The best cut-off for pretreatment Ki67 in predicting the connection with the tumor size lessening was 25.5% in luminal subtype. Aggressive adjuvant systemic treatments should be considered for patients with HER2-rich and triple-negative subtype who exhibit tumor shrinkage in NAC but still have high levels of Ki67.
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Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/genética , Receptor ErbB-2/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/classificação , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Receptores de Progesterona/genética , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
The design and synthesis of multifunctional chitosan hydrogels based on polymerized ionic liquid and a near-infrared (NIR) fluorescent probe (PIL-CS) is a promising strategy, which not only prevents the transition from acute to chronic wounds, but also provides prompt measures regarding microenvironmental alterations in chronic wounds. PIL-CS hydrogel can real-time visualize wound pH through in vivo NIR fluorescent imaging and also feature the pH-responsive sustained drug release, such as antioxidant, to eliminate reactive oxygen species (ROS) and to boost diabetic wound healing. PIL-CS hydrogel is specific, sensitive, stable, and reversible in response to pH changes at the wound site. It, therefore, enables real-time monitoring for a dynamic pH change in the microenvironment of irregular wounds. PIL-CS hydrogel is also designed to possess many merits including high water containment and swelling rate, good biocompatibility, electrical conductivity, antifreeze, tissue adhesion, hemostatic performance, and efficient antibacterial activity against MRSA. In vivo studies showed that PIL-CS hydrogel provided fast diabetic wound healing support, promoted vascular endothelial growth factor (VEGF) production, and reduced ROS and tumor necrosis factor (TNF-α) generation. The results support that the hydrogels coupled with NIR fluorescent probes can be an excellent diabetic wound dressing for enhancing and real-time monitoring skin restoration and regeneration.
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Diabetes Mellitus , Hidrogéis , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio , Fator A de Crescimento do Endotélio Vascular , Bandagens , Cicatrização , Corantes Fluorescentes , Antibacterianos/farmacologia , Concentração de Íons de HidrogênioRESUMO
Intussusception refers to the invagination of a proximal loop of the bowel into an adjacent distal segment. This condition is rare in adults, especially when it involves a complete folding of the ileocecal area out of the body cavity. Meanwhile, enterogenous cysts are congenital malformations that are largely identified in childhood following symptoms of bowel obstruction. While surgical treatment is ultimately required for both diseases, deciding on the type of surgery and the right time to operate can be a challenge for clinicians. It is especially difficult to decide on treatment for an adult with the coincidental occurrence of both conditions and no definitive pathologic diagnosis prior to surgery. Here, we present the case study of a 19-year-old female patient who presented with a prolapsed anus due to intussusception caused by a large ileocecal mass. The patient was admitted to the emergency department with a "massive anal mass." She remained symptomatic after receiving conventional conservative treatment and had to undergo emergency surgery after developing an intestinal obstruction. While the patient's intraoperative condition also confirmed the preoperative CT findings, the situation became more complicated during surgery. The postoperative pathological report indicated the presence of an enterogenous cyst. After recovery from surgery, the patient was successfully discharged. Intussusception or intestinal obstruction caused by an intestinal mass is a surgical indication, and removal is the only way to cure the condition. This case study provides a helpful reference for general surgeons, especially anorectal surgeons, imaging physicians, and pathologists, and informs the diagnosis and treatment of this patient population.
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OBJECTIVES: Large-scale epidemiological surveys have shown that patients with Down syndrome, which is caused by a chromosomal abnormality (an extra chromosome 21), are significantly less likely to develop solid tumors, including breast cancer, than those without. This feature has prompted the search for oncogenes located on chromosome 21. Junctional adhesion molecule 2 (JAM2), which is located on chromosome 21, is expressed at low levels in breast cancer and is associated with a good prognosis. These findings strongly suggest that JAM2 may be a potential oncogene suppressor in breast cancer. However, the role and function of JAM2 in breast cancer are not yet clear. Therefore, this study aimed to explore the biological functions and mechanisms of JAM2 in breast cancer. METHODS: Several databases were used to explore JAM2 expression in breast cancer and to analyze its diagnostic and prognostic value in breast cancer. Changes in relevant markers were examined at the gene and protein levels using RT-qPCR and Western blot techniques, in addition, cell migration and invasion abilities were identified by scratch assays and transwell assays. Untargeted metabolomics, transcriptome sequencing and Luminex liquid suspension chip detection were performed in combination to study the mechanisms. RESULTS: JAM2 is expressed at low levels in breast cancer, and patients with high JAM2 expression have a good prognosis, indicating that JAM2 has good clinical diagnostic and prognostic value. Overexpression of JAM2 can block the invasion and migration of breast cancer cells, and the mechanism may be that JAM2 inhibits the EMT pathway. Finally, combined multiomics analysis revealed that JAM2 may affect the immune microenvironment of breast cancer by influencing the secretion of CXCL9/10 from tumor cells.
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Neoplasias da Mama/diagnóstico , Moléculas de Adesão Celular/metabolismo , Cromossomos Humanos Par 21/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Moléculas de Adesão Celular/genética , Movimento Celular , Bases de Dados como Assunto , Transição Epitelial-Mesenquimal , Feminino , Humanos , Metabolômica , Invasividade Neoplásica , Prognóstico , Análise de Sobrevida , TranscriptomaRESUMO
Breast cancer patients show significant heterogeneity in overall survival. Current assessment models are insufficient to accurately predict patient prognosis, and models for predicting treatment response are lacking. We evaluated the relationship between various immune cells and breast cancer and confirmed the association between immune infiltration and breast cancer progression. Different bioinformatics and statistical approaches were combined to construct a robust immune infiltration-related gene signature for predicting patient prognosis and responses to immunotherapy and chemotherapy. Our research found that a higher immune infiltration-related risk score (IRS) indicates that the patient has a worse prognosis and is not very sensitive to immunotherapy. In addition, a new nomogram was constructed based on the gene signature and clinicopathological features to improve the risk stratification and quantify the risk assessment of individual patients. Our study might contribute to the optimization of the risk stratification for survival and the personalized management of breast cancer.
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Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Biologia Computacional , Tratamento Farmacológico , Feminino , Perfilação da Expressão Gênica , Humanos , Imunoterapia , Nomogramas , Prognóstico , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
HORMA domaincontaining protein 1 (HORMAD1), is normally expressed only in the germline, but is frequently reactivated in human triplenegative breast cancer (TNBC); however, its function in TNBC is largely unknown. In the present study, the expression and biological significance of HORMAD1 in human TNBC was evaluated. Bioinformatics analysis and reverse transcriptionquantitative PCR were used to evaluate HORMAD1 expression in datasets and cell lines. HORMAD1 protein expression was detected in TNBC samples using immunohistochemical assays, and the effect of HORMAD1 on cell proliferation was determined using Cell Counting Kit8, plate colony formation and standard growth curve assays. Cell cycle, reactive oxygen species (ROS) and apoptosis analyses were conducted using flow cytometry. The activity of caspases was measured using caspase activity assay kit. The levels of key apoptosis regulators and autophagy markers were detected by western blot analysis. TNBC cell survival and apoptosis were not influenced by small interfering RNA targeting HORMAD1 alone; however, HORMAD1 knockdown enhanced autophagy and docetaxel (Doc)induced apoptosis, compared with the control group. Furthermore, higher ROS levels and caspase3, 8 and 9 activity were detected in MDAMB436 TNBC cells with HORMAD1 knockdown upon exposure to Doc. The levels of the induced DNA damage marker γH2AX were also higher, while those of the DNA repair protein RAD51 were lower in TNBC cells with HORMAD1 knockdown compared with the controls. Furthermore, the expression of the autophagy marker P62 was enhanced in MDAMB231 cells in response to HORMAD1 overexpression. Notably, Docinduced apoptosis was similarly increased by both HORMAD1 overexpression and treatment with the autophagy inhibitor, 3methyladenine (3MA); however, the Docinduced increase in autophagy was not inhibited by 3MA. The present data indicated that HORMAD1 was involved in autophagy and that the inhibition of autophagy can partially enhance the induction of apoptosis by Doc. The role of HORMAD1 in the DNA damage tolerance of tumor cells may be the main reason for Doc resistance; hence, HORMAD1 could be an important therapeutic target in TNBC.
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Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Mama Triplo Negativas/patologia , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Dano ao DNA , Docetaxel/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Rad51 Recombinase/metabolismo , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Carga TumoralRESUMO
Following the publication of this article, the authors realized that the published version of Fig. 4A contained an erroneous label; essentially, the information purported to relate to experiments having been performed with docetaxel should not have been included in this figure. The correctly labelled version of Fig. 4 is shown with the remainder of Fig. 4 on the next page. This change does not affect the data shown in the paper, and the text in the published article did accurately describe the information shown in this figure. The authors sincerely apologize for the error that was introduced during the preparation of this figure, and thank the Editor for allowing them the opportunity to publish a Corrigendum. Furthermore, they regret any inconvenience caused. [the original article was published in Oncology Reports 46: Article no. 138, 2021; DOI: 10.3892/or.2021.8089].
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PURPOSE: The aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group. MATERIALS AND METHODS: Data from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan-Meier and Cox analyses. RESULTS: Ki67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135-3.658, P = 0.017; HR: 2.493, 95% CI: 1.335-4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173-4.077, P = 0.014; HR: 2.499, 95% CI: 1.285-4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475-8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512-9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively. CONCLUSION: Ki67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.
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Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients. We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of the immune microenvironment and the probability of a response to immunotherapy and chemotherapy. The patients were divided into a high-risk group and a low-risk group according to the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14-1.76, P = 0.002; HR, 2.19, 95% CI, 1.13-4.26, P = 0.02). Gene set enrichment analysis indicated that the term "cytokine-cytokine receptor interaction" was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, the low-risk group was much more sensitive to immunotherapy, and six drugs might have potential therapeutic implications in the high-risk group. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed favorable discriminative ability and could help guide clinical decision-making for luminal-type breast carcinoma.
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Neoplasias da Mama/genética , Ferroptose , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. METHODS: Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. RESULTS: SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial-mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. CONCLUSION: SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.
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Transição Epitelial-Mesenquimal/fisiologia , Serpinas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Regulação para CimaRESUMO
Centrosome amplification (CA) is a common feature of human tumors, but it is not clear whether this is a cause or a consequence of cancer. The centrosome amplification observed in tumor cells may be explained by a series of events, such as failure of cell division, dysregulation of centrosome cycle checkpoints, and de novo centriole biogenesis disorder. The formation and progression of breast cancer are characterized by genomic abnormality. The centrosomes in breast cancer cells show characteristic structural aberrations, caused by centrosome amplification, which include: an increase in the number and volume of centrosomes, excessive increase of pericentriolar material (PCM), inappropriate phosphorylation of centrosomal molecular, and centrosome clustering formation induced by the dysregulation of important genes. The mechanism of intracellular centrosome amplification, the impact of which on breast cancer and the latest breast cancer target treatment options for centrosome amplification are exhaustively elaborated in this review.
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Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Centrossomo/metabolismo , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Centrossomo/efeitos dos fármacos , Centrossomo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mitose , Terapia de Alvo Molecular , Via de Sinalização WntRESUMO
Tamoxifen (TAM) resistance is a major challenge in the treatment of estrogen receptorpositive (ER+) breast cancer. To date, to the best of our knowledge, there are only a few studies available examining the response of patients with TAMresistant breast cancer to chemotherapy, and the guidelines do not specify recommended drugs for these patients. In the present study, TAMresistant cells were shown to exhibit increased proliferation and invasion compared with the parent cells, and the increased expression of cMYC was demonstrated to play an important role in TAM resistance. Furthermore, the TAMresistant cells were significantly more sensitive to cisplatin compared with the parent cells, and the silencing of cMYC expression desensitized the cells to cisplatin through the inhibition of the cell cycle. An increased cMYC expression was observed in 28 pairs of primary and metastatic tumors from patients treated with TAM, and the clinical remission rate of cisplatinbased chemotherapy was significantly higher compared with other chemotherapybased regimens in 122 patients with TAM resistant breast cancer. Taken together, the data of the present study demonstrated that although cMYC was involved in TAM resistance, it increased the sensitivity of ER+ breast cancer to cisplatin. Thus, cisplatin may be a preferred chemotherapeutic agent for the treatment of patients with TAMresistant breast cancer, particularly in patients where the rapid control of disease progression is required.
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Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Tamoxifeno/farmacologia , Adulto , Antineoplásicos/farmacologia , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/genética , Resultado do TratamentoRESUMO
PURPOSE: Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. METHODS: A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. RESULTS: Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup. According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. CONCLUSION: High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients. These results are potentially considered beneficial in establishing treatment decisions.
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The combination of some parameters, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and neutrophil to monocyte ratio (NMR), which are associated with patient prognosis, our goal is to find the best indicator to predict the efficacy of neoadjuvant chemotherapyï¼NACï¼in breast cancer patients. A cohort of 808 breast cancer patients treated with NAC and subsequent surgery was analyzed retrospectively. In addition, 2424 people without breast cancer served as the normal group, which included three-fold more individuals compared with the breast cancer group. Receiver operating characteristics (ROC) curves were used to determine the optimal cutoff values of inflammatory markers and compare their predictive capacity. No significant differences in age, PLR, LMR and NMR were noted between the normal group and the patient group. However, the mean value of the NLR was significantly increased in breast cancer patients (2.28) compared with the normal population (2.04) (P < .05). The LMR was significantly associated with age (P = .003), menopausal status (P = .004), cT category (P = .017), cN category (P = .024) and response to NAC (P = .001). The multivariate analysis indicated that among these inflammatory markers, the LMR (6.1 < vs ≥ 6.1) was the only independent predictive factor for the efficacy of NAC (OR = 1.771, 95% CI = 1.273-2.464, P = .001). A low LMR is considered a favorable predicative factor of the efficacy of NAC in breast cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Linfócitos/patologia , Monócitos/patologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Plaquetas/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neutrófilos/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
Though proposed as a promising target antigen for cancer immunotherapy, the prognostic value of Wilms' tumor 1 (WT1) in solid tumors remains inconclusive. Here, we report a systematic review and meta-analysis of the association between WT1 expression and prognosis in solid tumors. PubMed, Web of Science and Google Scholar were searched to identify studies exploring the impact of WT1 on clinical outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), relapse/recurrence-free survival (RFS) or progression-free survival (PFS), in solid cancer patients. Hazard ratio (HR) and 95% confidence interval (CI) were applied to assess the strength of these associations. Finally, a total of 29 eligible studies with 4090 patients were identified for qualitative analysis, and 22 studies with 3620 patients were enrolled for quantitative synthesis. Overall, positive expression of WT1 was significantly associated with worse OS (metaHR = 1.48, 95% CI = 1.11-1.97) and DFS/RFS/PFS (metaHR = 2.14, 95% CI = 1.42-3.21). Subgroup analyses showed that WT1 positive expression could independently predict unfavorable DFS/RFS/PFS (metaHR = 1.86, 95%CI = 1.04-3.35). In summary, our study suggests that WT1 may be a potential marker to predict DFS/RFS/PFS in solid tumor patients. Further studies are needed to confirm the role of WT1 expression in clinical practice.
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Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Neoplasias/metabolismo , Neoplasias/mortalidade , Proteínas WT1/metabolismo , Comorbidade , Intervalo Livre de Doença , Humanos , Incidência , Recidiva Local de Neoplasia/diagnóstico , Neoplasias/diagnóstico , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taxa de SobrevidaRESUMO
Wilms' tumor gene 1 (WT1) single nucleotide polymorphism (SNP), rs16754, has been considered as an independent prognostic factor in patients with acute myeloid leukemia and renal cell carcinoma. However, its biological role in breast cancer has not been reported. To test whether WT1 SNPs can be used as a molecular marker in order to improve the risk stratification of breast cancer, we performed a case-control study including 709 female sporadic breast cancer patients and 749 female healthy control subjects in the Southeast China. Five WT1 SNPs (rs16754, rs3930513, rs5030141, rs5030317, rs5030320) were selected and determined by polymerase chain reaction-ligase detection reaction to assess their associations with breast cancer risk. Results showed the distributions of the alleles of these WT1 SNPs were consistent with data from Chinese population as suggested by the International HapMap Project. Individuals with the minor alleles of rs16754, rs5030317 and rs5030320 showed a significant decrease of breast cancer risk in codominant model (OR = 0.6370, 95% CI: 0.4260-0.9520 for rs16754; OR = 0.5940, 95% CI: 0.3890-0.9070 for rs5030317; OR = 0.5870, 95% CI: 0.3850-0.8960 for 5030320, respectively) and recessive model. Stratified analyses showed the protective effects were more evident in the subjects with age ≤ 50 years or in pre-menopausal status. To explore the potential mechanism, we conducted bioinformatics genotype-phenotype correlation analysis, and found that the mRNA expression level for homozygous rare allele of WT1 gene was lower than that in wild-type and heterozygous group (P = 0.0021) in Chinese population. In summary, our findings indicated that minor alleles of rs16754, rs5030317 and rs5030320 are associated with reduced risk of breast cancer, suggesting that WT1 SNPs may be a potential biomarker of individualized prediction of susceptibility to breast cancer. However, large prospective and molecular epidemiology studies are needed to verify this correlation and clarify its underlying mechanisms.