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
Objective Recently, the incidence of breast cancer has been the highest among female malignant tumors. Therefore, potential biomarkers are urgently needed to predict and prevent breast cancer. This study was aimed to explore the expression and clinical significance of differential miRNAs and their target genes in breast cancer by establishing miRNA expression profile in breast cancer tissues. Methods From January 2015 to December 2018, a total of 137 cases of breast cancer tissues with paired paracancerous tissues and 20 cases of breast fibroadenoma tissues were collected from the department of breast surgery, affiliated hospital of Guizhou Medical University. The tissues were divided into breast cancer group, paracancerous group, breast fibroadenoma group and lymph node metastasis group. High-throughput sequencing technique was used to detect the miRNAs in breast cancer tissues and paired paracancerous tissues. Real-time PCR verified the expressions of the three miRNAs with the most significant expression differences in different groups. Finally, bioinformatics analysis was used to predict the target genes and investigate the expression of miRNAs and proteins of target genes in different breast diseases. Results A total of 157 upregulated and 162 downregulated miRNAs were screened by high-throughput sequencing. Mir-hsa-miR-532-3p and hsa-miR-1260b were the most significant in upregulated miRNAs while has-let-7c-5p was the most significant in downregulated miRNAs. Meanwhile, bioinformatics analysis showed that their target gene was EZH2. Compared with para-cancerous group, expressions of hsa-miR-532-3p and hsa-miR-1260b were significantly upregulated while hsa-let-7c-5p was significantly down-regulated in breast cancer group and lymph node metastasis group (all P<0.05). The miRNA expressions of target gene EZH2 in breast cancer group, breast fibroadenoma group and lymph node metastasis group (1.24±0.01, 4.02±0.01, 15.97±0.01, respectively) were upregulated when compared with the para-cancerous group (1.00±0.00), and the similar conclusion could be drawn in EZH2 protein expression. Conclusion Hsa-miR-532-3p, hsa-miR-1260b and hsa-let-7c-5p were closely related to breast cancer, which may promote the occurrence and development of breast cancer by inducing the transcriptional expression of EZH2. HsamiR-532-3p, hsa-miR-1260b, hsa-let-7c-5p and EZH2 may be potential tumor biomarkers of breast cancer.