ABSTRACT
ObjectiveCasitas B-lineage lymphoma proto-oncogene (CBL) expression in different types of breast cancer and its role in the diagnosis and prognosis evaluation of breast cancer patients have been rarely reported. Here, we aimed to analyze the expression levels of CBL in breast cancer tissues and its difference in different molecular types, pathological types, TNM grades and clinical stages. Additionally, the role of CBL in the diagnosis and clinical prognosis evaluation in breast cancer patients was researched.MethodsData were downloaded from the USCS Xena database, and the expression of CBL genes in breast cancer tissues (1104 cases) and adjacent tissues (113 cases) were analyzed. CBL gene expression of different molecular types (triple negative, HER2+, Luminal A, Luminal B) and different pathological types (invasive ductal cancer, invasive lobular cancer, mixed tissue breast cancer, mucinous cancer, others) in breast cancer tissue samples were analyzed. It is divided into T1, T2, T3, T4, and Tx according to the tumor volume and the affected area of adjacent tissues. It is divided into N0, N1, N2, N3, and Nx according to the regional lymph node involvement. It is divided into cM0 (i+), M0, M1, Mx according to whether there is a distant transfer. According to different clinical stages, it is divided into stage I, stage II, stage III, stage IV, and others. Expression of CBL gene in different TNM grades and clinical stages of breast cancer was compared.Correlation between CBL gene expression and different TNM grades, clinical stages of breast cancer was examined. The ROC curve was used to evaluate the value of CBL in the diagnosis of breast cancer. According to the median value of gene expression 2.152, it was divided into high expression group (≥2.152) and low expression group (<2.152). Survival analysis was performed to verify whether CBL gene is associated with survival prognosis gene. The expression level of CBL protein in breast cancer tissues was further detected by immunohistochemistry.ResultsIn breast cancer tissues with different molecular types, the expression of CBL gene was highest in triple-negative breast cancer tissues (P<0.05). The expression of CBL gene in Luminal B breast cancer tissues was lower than that of Luminal A (P<0.05). The expression level of CBL gene in invasive ductal carcinoma, invasive lobular carcinoma and mucinous carcinoma tissues was lower than that in mixed tissue breast cancer (P<0.05). The expression level of CBL gene in invasive ductal carcinoma was higher than that of invasive lobular carcinoma (P<0.05). The expression of CBL gene from T1 to T3 gradually decreased (P<0.05). The expression of CBL gene in N0 was higher than that in N1 (P<0.05). The expression of CBL gene gradually decreased from stage Ⅰ to Ⅲ (P<0.05). The area under the ROC curve of CBL mRNA in breast cancer tissues for diagnosis was 0.768. The survival rate of the CBL gene high expression group was higher than low expression group (P<0.05). The CBL gene is a prognosis-related gene, and high expression of CBL is positively correlated with the good prognosis of breast cancer patients (P<0.05).ConclusionCBL is a good prognosis-related gene in breast cancer patients, and it is expected to become a new clinical diagnostic and prognostic marker for breast cancer patients.
ABSTRACT
BACKGROUND: Casitas B-lineage lymphoma proto-oncogene-b (CBLB) influences the threshold of T cell activation and controlling peripheral T cell tolerance. In the present study, we hypothesize that potentially functional single nucleotide polymorphisms (SNPs) in CBLB are associated with clinical outcomes in patients advanced non-small cell lung cancer (NSCLC) treated with the first-line chemotherapy. METHODS: We genotyped three SNPs (rs2305035, rs3772534 and rs9657904) at CBLB in 116 advanced NSCLC patients with progression free survival (PFS) data and 133 advanced NSCLC patients with overall survival (OS) data, and we assessed their associations, 95% confidence interval (CI), with clinical outcomes by using Cox proportional hazards regression analyses. In silico functional analysis was also performed for the SNPs under investigation. RESULTS: We found that associations between the three SNPs and PFS/OS were not significant in the overall NSCLC patients. The rs2305035 AA genotype was associated with a worse PFS in female patients and those of non-smokers or light smokers (95% CI, 1.14-11.81, P=0.030; 95% CI, 1.42-10.24, P=0.008; and 95% CI, 1.39-9.93, P=0.009; respectively), compared with the GG+AA genotypes. We also found that the rs9657904 CC genotype was significantly associated with a worse OS than TT + TC genotypes in male advanced NSCLC patients. Further in silico functional analysis revealed that the rs965704 T allele was significantly associated with lower mRNA expression levels of the CBLB gene. CONCLUSIONS: Our findings identified two CBLB SNPs (rs2305035 and rs9657904) that were significantly associated with PFS and OS in several subgroups of Chinese advanced NSCLC patients after the first-line chemotherapy.
ABSTRACT
Osteoclasts are the exclusive cells of bone resorption. Abnormally activating osteoclasts can lead to low bone mineral density, which will cause osteopenia, osteoporosis, and other bone disorders. To date, the mechanism of how osteoclast precursors differentiate into mature osteoclasts remains elusive. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in numerous cellular processes, including cell differentiation and apoptosis, by post-transcriptional regulation of genes. Recently, a number of studies have revealed that miRNAs participate in bone homeostasis, including osteoclastic bone resorption, which sheds light on the mechanisms underlying osteoclast differentiation. In this review, we highlight the miRNAs involved in regulating osteoclast differentiation and bone resorption, and their roles in osteoporosis.
