scholarly journals Diagnostic Value of LncRNAs for Postoperative Metastasis of Breast Cancer: A Nested Case-Control Study.

Author(s):  
Liyue Hao ◽  
Xiabin Li ◽  
Zhonghua Tao ◽  
Haisan Zheng ◽  
Bin Wu ◽  
...  

Abstract 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.

2021 ◽  
Author(s):  
Liyue Hao ◽  
xiabin li ◽  
zhonghua Tao ◽  
haisan Zheng ◽  
bin wu ◽  
...  

Abstract 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.


Author(s):  
Cheng Peng ◽  
Chi Gao ◽  
Donghao Lu ◽  
Bernard A Rosner ◽  
Oana Zeleznik ◽  
...  

ABSTRACT Background Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. Objectives We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses’ Health Studies (NHS and NHSII). Methods This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. Results We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8–42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7–52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. Conclusions The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.


2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Stephanie Scarmo ◽  
Yelena Afanasyeva ◽  
Per Lenner ◽  
Karen L Koenig ◽  
Ronald L Horst ◽  
...  

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