Abstract:Objective: To investigate the expression and clinical significance of microRNA (miRNA)-4732-5p and tetraspanin 13 (TSPAN13) mRNA in breast cancer tissues. Methods: Surgical specimens of 105 breast cancer patients hospitalized in our hospital from January 2017 to August 2018 were collected. QRT-PCR was performed to detect miR-4732-5p and TSPAN13 mRNA expression in cancer and paracancerous tissues. Pearson correlation analysis was used to aalyze the correlation between miR-4732-5p and TSPAN13 mRNA expression in breast cancer tissues, and their correlation with the clinicopathologic features. The K-M method was used to plot the survival curves of breast cancer patients with different miR-4732-5p and TSPAN13 mRNA expression, Multi-factor Cox regression analysis to analyze factors influencing poor prognosis in breast cancer patients.Results: Compared with paraneoplastic tissues, miR-4732-5p expression (0.629±0.169 vs. 1.131±0.273) was elevated and TSPAN13 mRNA expression (0.529±0.081 vs. 0.355±0.078) was decreased in breast cancer tissues, with statistical differences (t=16.019, -15.790, both P<0.001). Pearson correlation analysis showed a negative correlation between miR-4732-5p and TSPAN13 mRNA expression in breast cancer tissues (r=-0.732, P<0.001). The expression of miR-4732-5p and TSPAN13 mRNA was associated with the degree of breast cancer differentiation, TNM stage, and lymph node metastasis (P<0.05 ). At 3 years follow-up, a median of 28 months, the cumulative survival rate of 105 breast cancer patients was 87.62% (92/105). The cumulative survival rate of the high miR-4732-5p expression group was lower than that of the low miR-4732-5p expression group, and the cumulative survival rate of the high TSPAN13 mRNA expression group was higher than that of the low TSPAN13 mRNA expression group (P<0.05). Multi-factorial Cox regression analysis showed that TNM stage III-IV (HR=3.381, 95% CI: 1.658 to 5.377, P=0.018), lymph node metastasis (HR=4.546, 95% CI: 1.870 to 7.758, P=0.011), miR-4732-5p≥1.131 (HR=2.932. 95% CI: 1.482 to 4.770, P=0.015) were independent risk factors for poor prognosis and TSPAN13 mRNA ≥0.355 (HR=0.310, 95% CI: 0.156 to 0.729, P=0.044) were independent protective factors for breast cancer patients.Conclusion: Upregulation of miR-4732-5p expression and downregulation of TSPAN13 mRNA expression in breast cancer tissues correlate with differentiation, TNM stage and lymph node metastasis and may be a prognostic assessment biomarker for breast cancer patients.
[1] Cao W,Chen HD,Yu YW,et al.Changing profiles of cancer burden worldwide and in China:a secondary analysis of the global cancer statistics 2020[J].Chin Med (Engl),2021,134(7):783~791. [2] 国家肿瘤质控中心乳腺癌专家委员会,中国抗癌协会乳腺癌专业委员会,中国抗癌协会肿瘤药物临床研究专业委员会.中国晚期乳腺癌规范诊疗指南(2020版)[J].中华肿瘤杂志,2020,42(10):781~797. [3] Zhang K,Zhao S,Wang Q,Y et al.Identification of microRNAs in nipple discharge as potential diagnostic biomarkers for breast cancer[J].Ann Surg Oncol,2015,22(Suppl 3):S536~S544. [4] Jiang L,Zhang X,Geradts J,et al.Expression of tetraspanins NET-6 and CD151 in breast cancer as a potential tumor biomarker[J].Clin Exp Med,2019,19(3):377~384. [5] Thill M,Friedrich M,Kolberg-Liedtke C,et al AGO recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer:update 2021[J].Breast Care (Basel),2021,16(3):228~235. [6] Omura T,Shimada Y,Nagata T,et al.Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy[J].Oncol Rep,2014,31(2):613~618. [7] Liu J,Yoo J,Ho JY,et al.Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer[J].Ovarian Res,2021,14(1):59. [8] 谢林峰,向俊蓓,姜欣.突变p53在肿瘤发生过程中的功能研究与进展[J].中国医学创新,2020,17(24):169~172. [9] Pouladi N,Kouhsari SM,Feizi MH,et al.Overlapping region of p53/wrap53 transcripts:mutational analysis and sequence similarity with microRNA-4732-5p[J].Asian Pac Cancer Prev,2013,14(6):3503~3507. [10] Florin L,de Winde CM.Recent advancements in the understanding of tetraspanin functions[J].Med Microbiol Immunol,2020,209(4):393~395. [11] Li P,Dong M,Wang Z.Downregulation of TSPAN13 by miR-369-3p inhibits cell proliferation in papillary thyroid cancer (PTC) [J].Bosn Basic Med Sci,2019,19(2):146~154. [12] Jaiswal RK,Kumar P,Kumar M,et al.hTERT promotes tumor progression by enhancing TSPAN13 expression in osteosarcoma cells[J].Mol Carcinog,2018,57(8):1038~1054. [13] Wang YW,Zhao S,Yuan XY,et al.miR-4732-5p promotes breast cancer progression by targeting TSPAN13[J].Cell Mol Med,2019,23(4):2549~2557.