PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was –0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >–0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.
Breast Neoplasms* ; Breast* ; Cell Line ; Disease-Free Survival* ; Drug Therapy ; Humans ; In Vitro Techniques ; Methods ; Neoadjuvant Therapy ; Paclitaxel ; Porifera ; Prognosis ; Retrospective Studies ; RNA, Long Noncoding

Objective:To analyze the risk factors for lymph node metastasis in breast cancer patients with axillary lymph node metastasis after neoadjuvant chemotherapy.Methods:The data of 94 female patients with invasive breast cancer in Dongguan People′s Hospital of Guangdong Province from January 2017 to December 2019 were retrospectively analyzed.All patients planned to receive 4-8 cycles of neoadjuvant chemotherapy.After chemotherapy, modified radical mastectomy was performed.Estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor 2(HER-2) appeared for the first time in Chinese and English abstracts and texts positive patients received endocrine or targeted therapy.The rest patients received 2-4 cycles of adjuvant chemotherapy or radiotherapy according to the situation.Lymph node metastasis after neoadjuvant chemotherapy was analyzed.The relationship between lymph node metastasis after neoadjuvant chemotherapy and clinicopathological features was analyzed.Risk factors for lymph node metastasis after neoadjuvant chemotherapy were analyzed by Logistic regression.Results:After neoadjuvant chemotherapy, the positive rate of axillary lymph node was 74.47%(70/94). The number of positive axillary lymph nodes, ER status, HER-2 status and cell proliferation-associated human nuclear antigen(Ki67), the completion of chemotherapy cycle, the pathological remission of axillary lymph nodes after chemotherapy and the T stage of tumor after neoadjuvant chemotherapy were associated with lymph node metastasis in patients with positive axillary lymph nodes after neoadjuvant chemotherapy(χ 2=30.053, 10.233, 6.303, 7.666, 18.162, 10.148, 12.418; all P<0.05). More than 3 positive axillary lymph nodes( OR=2.788, 95% CI 1.253-5.318), ER positive( OR=3.298, 95% CI 1.744-7.837), Ki67 positive( OR=2.469, 95% CI 1.184-4.301)and pathological pPR( OR=4.197, 95% CI 2.168-13.788) were independent risk factors for lymph node metastasis after neoadjuvant chemotherapy(all P<0.05). Conclusion:Axillary lymph node-positive breast cancer patients have a high positive rate of axillary lymph nodes after neoadjuvant chemotherapy.More than 3 positive axillary lymph nodes before operation, ER positive, Ki67 positive, and axillary lymph node pPR after neoadjuvant chemotherapy are independent risk factors for lymph node metastasis after neoadjuvant chemotherapy.