RESUMO
Previous studies have indicated that cancer patients may have a lower level of subjective well-being (SWB); nevertheless, the underlying factors for this phenomenon remain insufficiently investigated. Based on the characteristics of Chinese breast cancer patients and the unique culture, this study explored the independent contributions of death anxiety, self-esteem, and social support to SWB from the protective and risk perspectives. A cross-sectional survey recruited 514 females with breast cancer and collected participants' demographic and the above variables. The results found that death anxiety independently predicted SWB in a negative direction (ß = -0.36, p < 0.001). In addition, self-esteem (ß = 0.38, p < 0.001) and social support (ß = 0.14, p < 0.001) also had the unique positive effects on SWB. These findings offer new insights into strengthening breast cancer patients' SWB, for instance, using relevant interventions to reduce death anxiety and improve self-esteem and social support.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Estudos Transversais , Apoio Social , Ansiedade , ChinaRESUMO
The prognosis of patients with gastric cancer (GC) is still unsatisfying. Numerous markers of gastric cancer stem cells (GCSCs) have been identified and were thought to be related to cancer aggressiveness. However, the roles of GCSC markers in GC patients' prognosis and immune infiltration remain unknown. Expression of GCSC markers was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). Their associations with clinicopathological parameters were analyzed using UALCAN and LinkedOmics. Alternations and protein expression of GCSC markers were analyzed by cBioPortal and the Human Protein Atlas databases, respectively. The prognostic significance of GCSC markers was evaluated using Kaplan-Meier plotter. Correlations between the expression of GCSC markers and immune infiltration along with biomarkers of tumor-infiltrating immune cells (TIICs) were assessed combined Tumor Immune Estimation Resource and GEPIA. GeneMANIA was used to discover the interactive genes of GCSC markers, and enrichment analysis was performed using Database for Annotation, Visualization, and Integrated Discovery server. We identified six GCSC markers significantly up-expressed in GC, compared with normal stomach tissues. Among them, the overexpression of ICAM1, THY1, and CXCR4 significantly indicated adverse, while EPCAM indicated beneficial clinicopathological features of GC patients. The up-regulation of CXCR4 showed unfavorable prognostic significance, whereas EPCAM and TFRC showed the opposite. The six GCSC markers were all correlated with the infiltration and activation of distinct TIICs. Especially, ICAM1, THY1, and CXCR4 showed strongly positive correlations with tumor-associated macrophages. Besides, chemokine, Toll-like receptor, NF-kappa B, and HIF-1 signaling pathways might be involved in the regulation of GCSC markers on cancer development. This study proposed that GCSC markers might be promising targets of GC treatment to weaken cancer stem-like properties and strengthen anticancer immunity.
RESUMO
BACKGROUND: The heat shock protein 90 (HSP90s) family is composed of molecular chaperones composed of four isoforms in humans, which has been widely reported as unregulated in various kinds of cancers. Nevertheless, the role of each HSP90s isoform in prognosis and immune infiltration in distinct subtypes of breast cancer (BRAC) remains unclear. METHODS: Public online databases including the Oncomine, UALCAN, Kaplan-Meier Plotter, Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GeneMANIA, and Database for Annotation, Visualization, and Integrated Discovery (DAVID) were integrated to perform bioinformatic analyses and to explore the possible associations among HSP90s gene expression, prognosis, and immune infiltration in BRAC. RESULTS: The mRNA expression of all HSP90s members was elevated in distinct clinical stages and subtypes of BRAC, compared with the normal breast tissue (P < 0.05). Overexpressed HSP90AA1 was associated with poor prognosis, particularly, both short overall survival (OS) and release-free survival (RFS) in Basal-like BRAC patients; overexpressed HSP90AB1 and HSP90B1 were both associated with poor RFS in Luminal A BRAC patients, while overexpressed TRAP1 was associated with favorable RFS in Luminal A BRAC patients. Moreover, HSP90s gene expression in BRAC showed correlations with the infiltration of CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs), as well as the activation of tumor-associated macrophages (TAMs), DCs, and CD4+ helper T (Th) cells. The underlying mechanisms of HSP90s modulating tumor-infiltrating immune cells (TIICs) might be related with their functions in antigen processing and presentation, major histocompatibility complex (MHC) binding, and assisting client proteins. CONCLUSION: This study demonstrated that HSP90s family genes were overexpressed and might be serve as prognostic biomarkers in subtypes of BRAC. It might be a novel breakthrough point of BRAC treatment to regulate immune infiltration in BRAC microenvironment for more effective anticancer immunity through pharmacological intervention of HSP90s.
Assuntos
Adenocarcinoma Mucinoso/genética , Neoplasias da Mama/genética , Carcinoma Ductal/genética , Carcinoma Lobular/genética , Proteínas de Choque Térmico HSP90/genética , Glicoproteínas de Membrana/genética , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/patologia , Atlas como Assunto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Ductal/diagnóstico , Carcinoma Ductal/imunologia , Carcinoma Ductal/patologia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/imunologia , Carcinoma Lobular/patologia , Movimento Celular , Biologia Computacional/métodos , Bases de Dados Genéticas , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP90/imunologia , Humanos , Glicoproteínas de Membrana/imunologia , Anotação de Sequência Molecular , Invasividade Neoplásica , Prognóstico , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/patologiaRESUMO
Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation.