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 explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.