TJP3 promotes T cell immunity escape and chemoresistance in breast cancer: a comprehensive analysis of anoikis-based prognosis prediction and drug sensitivity stratification.

BACKGROUND: Overcoming anoikis is a necessity during the metastasis and invasion of tumors. Recently, anoikis has been reported to be involved in tumor immunity and has been used to construct prognosis prediction models. However, the roles of anoikis in regulating tumor immunity and drug sensitivity in breast cancer are still not clear and therefore worth uncovering. METHODS: TCGA and GEO data are the source of gene expression profiles, which are used to identify anoikis-related-gene (ARG)-based subtypes. R4.2 is used for data analysis. RESULTS: Breast cancer is divided into three subgroups, amongst which shows prognosis differences in pan-cancer cohort, ACC, BLCA, BRCA, LUAD, MESO, PAAD, and SKCM. In breast cancer, it shows significant differences in clinical features, immune cell infiltration and drug sensitivity. Machine learning constructs prognosis prediction model, which is useful to perform chemotherapy sensitivity stratification. Following, TJP3 is identified and verified as the key ARG, up-regulation of which increases tolerance of paclitaxel-induced cell toxicity, accompanied with increased expression of caspas3 and cleaved-caspase3. In addition, Down-regulation of TJP3 weakens the cell migration, which accompanied with increased expression of E-cad and decreased expression of vimentin, twist1, zeb1, and MMP7. Furthermore, the expression level of PD-L1 is negative correlated with TJP3. CONCLUSION: ARGs-based subgroup stratification is useful to recognize chemotherapy sensitive cohort, and also is useful to predict clinical outcome. TJP3 promotes chemoresistance, tumor metastasis and potential immunotherapy escape in breast cancer.

The relationship between four GWAS-identified single nucleotide polymorphisms and female breast canc-er in Henan population / 中华内分泌外科杂志

Objective To verify the association between common breast cancer susceptibility loci which have been confirmed in European and Asian populations and breast cancer susceptibility in sporadic breast cancer among the Han nationality in Henan province , and to analyze their genotypes in the internal type of breast cancer . Methods In 253 breast cancer patients ( the case group ) and 343 patients who had benign breast lesions ( the control group), rs2046210(6q25.1), rs2981582(EGFR2), rs889312(MAP3K1), and rs3803662(TOX3/TNRC9)were genotyped by SNP im-LDR technique.According to estrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER2)and Ki67, breast cancer are divided into 5 types:Lu-minal A, Luminal B, HER2-enrich, Luminal HER2, and triple negative breast cancer ( TNBC).Results rs2046210(6q25.1), rs2981582(EGFR2), rs889312(MAP3K1)had no statistical differences between the case group and the control group(P=0.421, 0.459, and 0.468), but the genotype of rs3803662(TOX3/TNRC9)in the case group and the control group had statistical difference (P=0.037).The allelic frequencies of rs3803662 between the case group and control group were different in codominant inheritance ( OR=2.19, 95%CI:1.19-4.02)and recessive genetic models (OR =2.06,95% CI:1.15 -3.70).Compared with AA and GA, GG in-creased the risk of breast cancer ( P =0.012, 0.015 ).The genotypes of rs2046210 ( 6q25.1 ), rs2981582 (EGFR2), rs889312(MAP3K1), and rs3803662(TOX3/TNRC9)had no difference in different types of breast cancer.Conclusions Four common breast cancer susceptibility loci from GWAS are not entirely associated with breast cancer risk among the Han nationality in Henan province .Only rs3803662(TOX3/TNRC9)is confirmed to increase the risk of breast cancer .Different genotypes of 4 loci distribute equally in different types of breast cancer .

Expression of HIF-1α, Glut-1 and VEGF in breast cancer tissue in diabetic patients and its significance / 中华内分泌外科杂志

Objective To discuss the protein level of hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter-1 (Glut-1)and vascular endothelial growth factor(VEGF) in breast cancer tissue in diabetic patients and its significance.Methods HIF-1α,Glut-1 and VEGF protein levels were measured by immunohistochemical staining in 112 cases of primary breast cancer tissues.CD31 labeled vascular endothelial cells were used to evaluate micro vascular density (MVD).The correlation between the effect of blood sugar control and clinicopathological parameters was analyzed.Results The expression of HIF-1α,Glut-1 and VEGF protein in breast cancer tissues of diabetic patients was significantly higher than that in breast cancer tissues of non-diabetic patients(t =2.255,P =0.030; t =2.154,P=0.038; t =2.225,P =0.032).HIF-1α was positively correlated with Glut-1 and VEGF in diabetic patients with breast cancer (r =0.561,P =0.003 ; r =0.435,P =0.014).The level of MVD in breast cancer tissues of diabetic patients was obviously higher than that in the non-diabetic patients with breast cancer(t =9.458,P =0.000).The effect of blood sugar control was significantly correlated with lymph node metastasis and tumor stage in diabetic patients with breast cancer(x2 =4.689,P =0.030; x2 =5.051,P =0.025).Conclusion Hypoxia-related factors including HIF-1α,Glut-1 and VEGF and MVD are upregulated in diabetic patients with breast cancer,and the effect of blood sugar control is correlated with lymph node metastasis and tumor stage,suggesting diabetes mellitus may promote tumor progression through high glucose and hypoxia in breast cancer.

Relationship between RAD51 135G ＞ C polymorphism and prognosis in triple-negative breast cancer patients / 中华内分泌外科杂志

Objective To investigate the relationship between RAD51 135G ＞ C polymorphism and prognosis in triple-negative breast cancer patients by retrospective analysis.Methods The clinical data of 62 triplenegative breast cancer patients were collected.The 62 cases underwent standard chemotherapy and radiotherapy after tumor resection from Jan.2004 to Dec.2010 in Affiliated Cancer Hospital of Zhengzhou University.RAD51 135G ＞ C polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) technology.The survival curve about progress free and overall survival time were then made.Results The median progress free and overall survival time in triple-negative breast cancer patients with or with-out RAD51 135G ＞ C polymorphism were(77.00 ±5.55)and(89.00 ± 10.40) months vs(99.00 ±4.26)and (103.00 ±4.30) months.The difference had statistical significance(P =0.039 and 0.015 respectively).Conclusion RAD51 135G ＞ C polymorphism is related with prognosis of triple-negative breast cancer patients,which might be a prognostic factor for breast cancer.