Breast cancer is the most common malignant tumor in China and even in the world. DNA repair genes can lead to tumor metastasis by affecting cancer cell resistance. Studies have preliminarily shown that DNA repair genes are related to breast cancer metastasis, but it is not clear whether they can be used as a prediction of the risk of breast cancer metastasis. Therefore, this study mainly discusses the predictive value of DNA repair genes in postoperative metastasis of breast cancer. The nested case–control method was used in patients with breast cancer metastasis after surgery (n = 103) and patients without metastasis after surgery (n = 103). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. In protein expression, PARP1 (OR 1.147, 95% CI 1.067 ~ 1.233, P < 0.05), XRCC4 (OR 1.088, 95% CI 1.015 ~ 1.166, P < 0.05), XRCC1 (OR 1.114, 95% CI 1.021 ~ 1.215, P < 0.05), ERCC1 (OR 1.068, 95% CI 1.000 ~ 1.141, P < 0.10) were risk factors for postoperative metastasis of breast cancer. In addition, we used the ROC curve to study the optimal critical values of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA combined with the Youden index, and the effects of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA on breast cancer metastasis were verified again. Among them, the risk of metastasis in the PARP1 high expression group was 3.286 times that of the low expression group (OR 3.286, 95% CI 2.013 ~ 5.364, P < 0.05). The risk of metastasis in the XRCC4 high expression group was 1.779 times that of the low expression group (OR 1.779, 95% CI 1.071 ~ 2.954, P < 0.05). The risk of metastasis in patients with ERCC1 high expression group was 2.012 times that of the low expression group (OR 2.012, 95% CI 1.056 ~ 3.836, P < 0.05). So we can conclude that protein expression of PARP1 (cut-off value = 6, Se = 76.70%, Sp = 79.61%), XRCC4 (cut-off value = 6, Se = 78.64%0, Se = 79.61%), ERCC1 (cut-off value = 3, Se = 89.32%, Sp = 50.49%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of metastasis will increases. Due to PARP1, XRCC4 and ERCC1 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-XRCC4 = 0.343; rPAPR1-ERCC1 = 0.335; rXRCC4-ERCC1 = 0.388). The combined diagnosis of the PARR1, XRCC4 and ERCC1 have greater predictive value for the risk of metastasis of breast cancer (Se = 94.17%, Sp = 75.73%; OR 11.739, 95% CI 2.858 ~ 40.220, P < 0.05). The postoperative metastasis of breast cancer could be effectively predicted when the immunohistochemical scores met PARP1 (IHC score) > 6, XRCC4 (IHC score) > 6 and ERCC1 (IHC score) > 3. In addition, the combined diagnosis of PARP1, XRCC4 and ERCC1 has great predictive value for the risk of breast cancer metastasis.
Previous studies have reported the potential developmental neurobehavioral effects of decabrominated diphenyl ethers (BDE 209) on developing animals, but the effects on adult animals are rare or controversial and the mechanism is not fully understood. In the present study, male adult Sprague-Dawley rats performed poor spatial learning and memory in Morris water maze after exposure to BDE 209 by gavage for 30 days. The expression of hippocampal glutamate receptor subunits NR1, NR2B and GluR1, the phosphorylation of NR2B subunit at Ser1301 (p-NR2B Ser1303) and GluR1 subunit at Ser831 (p-GluR1 Ser831) were all decreased, and the phosphorylation ratio of NR2B revealed an increasing trend after BDE 209 exposure. The present study provided evidence that BDE 209 could induce spatial learning and memory deficits in adult rats, and further explored the potential mechanism.
Background: DNA repair genes play a vital role in the treatment of many cancers, and DNA repair genes can be used in breast cancer recurrence and metastasis research. We found that the expression of DNA repair genes in breast cancer patients after recurrence and metastasis is abnormal, however, the clinical predictive significance of DNA repair genes is still elusive. Methods: The nested case-control method was used in patients with breast cancer recurrence and metastasis after surgery (n=109) and patients without recurrence and metastasis after surgery (n=109). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. Results: PARP1(OR=1.485, 95%CI:1.279~1.725, P<0.05), XRCC4(OR= 1.419, 95%CI:1.217~ 1.656, P<0.05) and ERCC1 (OR=1.181, 95%CI: 1.032~1.353, P<0.05) were risk factors for postoperative recurrence and metastasis of breast cancer. Therefore, we used the ROC curve to study the optimal critical values of PARP1, XRCC4, and ERCC1, combined with the comprehensive judgment of clinical experience, we can conclude that PARP1 (cutoff value = 6, Se = 75.23%, Sp = 79.82%), XRCC4 (cutoff value = 6, Se = 78.9%0, Se = 79.82%), ERCC1 (cutoff value = 3, Se = 89.91%, Sp = 47.71%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of recurrence and metastasis will increases (ORPARP1 = 14.941, 95% CIPARP1: 4.004~55.758, P <0.05; ORXRCC4 = 16.740, 95% CIXRCC4: 6.433 ~ 43.560, P <0.05; ORERCC1 = 5.285, 95% CIERCC1: 1.843 ~ 15.156, P <0.05). Due to PARP1, ERCC1 and XRCC4 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-ERCC1=0.317; rPAPR1-XRCC4=0.329; rERCC1-XRCC4=0.377). The combined diagnosis of the PARR1,ERCC1 and XRCC4 have greater predictive value for the risk of recurrence and metastasis of breast cancer(Se = 88.99%, Sp = 82.57%;OR = 50.914, 95% CI: 10.918, 237.417, P <0.05).Conclusions: The recurrence and metastasis of breast cancer are predictive after PARP1>6, XRCC4>6, and ERCC1>3. The combined diagnosis of the three indicators have greater predictive value for the risk of recurrence and metastasis of breast cancer.
Background: Breast cancer is an aggressive tumor with no definitely identified prognostic biomarker for diagnosis. Studies have preliminarily found that lncRNAs are closely related to breast cancer metastasis, but, the significant clinical prediction of lncRNAs was remain unclear. In this study, we evaluated the diagnostic value of long non-coding RNA (lncRNA UCA1,CCAT2, ANCR) on postoperative metastasis of breast cancer as well as the possible mechanism involving the EMT.Methods: We investigated lncRNA ANCR, UCA1,CCAT2 are at high stake of breast cancer metastasis in a population-based nested case-control study. Metastasis cases were identified by clinical diagnostic criteria in approximately 103 cases in the Cancer Institute of Southwest Medical University during 2013-2020. Meanwhile, the control group (no-metastasis) was single out on the basis of the 1:1 pairing principle in this cohort (n=103, the matching condition was the surgery time within the same month, and the treatment plan both are modifed radical mastectomy ,age±3 years) The mRNA of lncRNA( UCA1,CCAT2, ANCR) expression was determined by Real-time PCR. By Western blot, the expression of E-cadherin, N-cadherin, and vimentin proteins was detected. The migration and invasion of transfected cells were determined by the Transwell assay.Results: lncRNA ANCR,UCA1,CCAT2 was significantly up-regulated in breast cancer cells and postoperative metastasis of breast cancer.CCAT2 (OR=1.024, 95% CI:1.010, 1.039), UCA1(OR=1.025, 95% CI: 1.011, 1.039),ANCR(OR=1.055, 95% CI:1.001, 1.111)was the risk factor for postoperative metastasis of breast cancer. Further more , By the ROC curve assay, we detect the optimal critical values of CCAT2, UCA1, ANCR , the risk of metastasis in the CCAT2 high expression group was 2.297 times that of the low expression group (OR=2.297, 95% CI:1.427 ~ 3.695, P< 0.05). The risk of metastasis in the UCA1 high expression group was 2.032 times that of the low expression group (OR=2.032, 95% CI 1.282 ~ 3.218, P<0.05). We further observed that lncRNA UCA1, CCAT2, ANCR was down-regulated in MDA-231 cells by 48 h of siRNA transfection. LncRNAs UCA1, CCAT2, ANCR silencing significantly decreased the migration and invasion cells, down-regulated N-cadherin, and up-regulated E-cadherin and vimentin in MDA-231 cells.Conclusions: Our data suggested that lncRNA CCAT2 ,UCA1,ANCR was a novel molecule involved in postoperative metastasis of breast cancer, which has predictive value in patients with breast cancer metastasis.
Background: Breast cancer is a malignancy with no clearly identified prognostic factors for diagnosis. Studies have preliminarily found that lncRNAs are related to breast cancer metastasis, however, the clinical predictive significance of lncRNAs is still elusive.In this study, we evaluated the diagnostic value of long non-coding RNA (lncRNA UCA1,CCAT2, ANCR) on postoperative metastasis of breast cancer as well as the possible mechanism involving the EMT. Methods: We investigated lncRNA ANCR, UCA1,CCAT2 that associated with breast cancer metastasis risk in a population-based nested case-control study. Metastasis cases were identified by clinical diagnostic criteria in approximately 103 cases in the Cancer Institute of Southwest Medical University during 2013-2020. At the same time, the control group (metastasis-free) was selected according to the 1:1 pairing principle in this cohort (n=103, the matching condition was age±3 years, the operation time within the same month, and the treatment plan both are modifed radical mastectomy) The mRNA of lncRNA( UCA1,CCAT2, ANCR) expression was determined by Real-time PCR. The expression of E-cadherin, N-cadherin, and vimentin proteins was detected by Western blot. The migration and invasion of transfected cells were determined by the Transwell assay.Results: lncRNA ANCR, UCA1, CCAT2 was significantly up-regulated in breast cancer cells and postoperative metastasis of breast cancer.CCAT2 (OR=1.024, 95% CI: 1.010, 1.039), UCA1(OR=1.025, 95% CI: 1.011, 1.039),ANCR(OR=1.055, 95% CI:1.001, 1.111)was the risk factor for postoperative metastasis of breast cancer. Furthermore , we used the ROC curve to detect the optimal critical values of CCAT2, UCA1, ANCR , the risk of metastasis in the CCAT2 high expression group was 2.297 times that of the low expression group (OR=2.297, 95% CI:1.427 ~ 3.695, P< 0.05). The risk of metastasis in the UCA1 high expression group was 2.032 times that of the low expression group (OR=2.032, 95% CI 1.282 ~ 3.218, P<0.05). We further observed that lncRNA UCA1, CCAT2, ANCR was down-regulated in MDA-231 cells by 48 h of siRNA transfection. LncRNAs UCA1, CCAT2, ANCR silencing significantly decreased the percentage of migration and invasion cells, down-regulated N-cadherin, and up-regulated E-cadherin and vimentin in MDA-231 cells.Conclusions: Our data suggested that lncRNA CCAT2 , UCA1,ANCR was a novel molecule involved in postoperative metastasis of breast cancer, which has predictive value in patients with breast cancer metastasis.
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