BackgroundTo investigate the roles of miR-17-5p/RRM2 in A549/G+. MethodsCell survival was analyzed by CCK8 kit and clone formation experiment; The mRNA expression level was detected by qRT-PCR, and the protein level was compared by Western blotting; And ow cytometry for cell cycle detection; The target gene of miR-17-5p was veri ed by double luciferase activity experiment. ResultsCCK8 assay displayed that miR-17-5p's overexpression can let A549/G + cells turn into sensitive ones; in turn, in the case of inhibition of expression, miR-17-5p can make A549/G-cells turn into resistance ones.And similar results were obtained in cell clone formation experiment. Cell cycle analysis showed that miR-17-5p's overexpression increased the number of G 1 phase cells and reduced the number of S phase cells in A549/G + cells; Conversely, lowing expression level of miR-17-5p yielded the opposite results in A549/G-cells. Western blot results showed that when miR-17-5p was expressed highly, the expression levels of cell cycle related proteins, CCNE1, CCNA2 and P21 decreased in A549/G + cells; Conversely, inhibition of miR-17-5p expression yielded the opposite results too in A549/G-cells. Western blot analysis of signal pathway proteins and the results showed that PTEN and PI3K expressed higher, but p-PTEN expressed lower in A549/G + cells. After miR-17-5p overexpressed in A549/G + cells, the level of p-PTEN increased, and the level of p-AKT decreased; when miR-17-5p expressed low in A549/G-cells, the expression of p-PTEN and p-AKT were opposite. The dual-luciferase experiment demonstrated that RRM2 was the target gene of miR-17-5p. The restorative experiments of RRM2 veri ed it. ConclusionThis article suggested that the miR-17-5p/RRM2 axis could adjust gemcitabine-resistance in A549 cells and might associate with p-PTEN/PI3K/AKT signal pathway.

The iron-related homeostasis and inflammatory biomarker have been identified as prognostic factors for cancers. We aimed to explore the prognostic value of a novel comprehensive biomarker, the iron-monocyte-to-lymphocyte ratio (IronMLR) score, in patients with early-stage triple-negative breast cancer (TNBC) in this study. We retrospectively analysed a total of 257 early-stage TNBC patients treated at Sun Yat-sen University Cancer Center (SYSUCC) between March 2006 and October 2016. Their clinicopathological information and haematological data tested within 1 week of the diagnosis were collected. According to the IronMLR score cutoff value of 6.07 μmol/L determined by maximally selected rank statistics, patients were stratified into the low- and high-IronMLR groups, after a median follow-up of 92.3 months (95% confidence interval [CI] 76.0–119.3 months), significant differences in 5-years disease-free survival (DFS) rate (81.2%, 95% CI 76.2%–86.5% vs. 65.5%, 95% CI 50.3%–85.3%, p = 0.012) and 5-years overall survival (OS) rate (86.0%, 95% CI 81.6%–90.7% vs. 65.5%, 95% CI 50.3%–85.3%, p = 0.011) were seen between two groups. Further multivariate Cox regression analysis revealed the IronMLR score as an independent predictor for DFS and OS, respectively, we then established a prognostic nomogram integrating the IronMLR score, T stage and N stage for individualized survival predictions. The prognostic model showed good predictive performance with a C-index of DFS 0.725 (95% CI 0.662–0.788) and OS 0.758 (95% CI 0.689–0.826), respectively. Besides, calibration curves for 1-, 3-, 5-DFS, and OS represented satisfactory consistency between actual and nomogram predicted survival. In conclusion, the Iron-inflammation axis might be a potential prognostic biomarker of survival outcomes for patients with early-stage TNBC, prognostic nomograms based on it with good predictive performance might improve individualized survival predictions.

Background Despite significant survival improvement in human epidermal growth factor receptor 2 (HER2) blockade for HER2-positive breast cancer, resistance to anti-HER2 remains inevitable. Subsequent anti-HER2 with continuing trastuzumab beyond progression is acceptable with limited efficacy when other anti-HER2 treatment is unavailable. This single-arm, phase II study (SYSUCC-005) aimed to explore the efficacy of switching mode for HER2-positive refractory metastatic breast cancer. Methods Patients with HER2-positive metastatic breast cancer rapidly progressing during pre-trastuzumab from six hospitals in China were designed to switch to lapatinib 1,250 mg orally once per day continuously plus capecitabine (1,000 mg/m2 orally twice per day on days 1–14) or vinorelbine (25 mg/m2 intravenously once per day on days 1 and 8) of each 21-day cycle. The primary endpoint was progression-free survival (PFS). Results Between January 5, 2015 and May 31, 2020, 159 patients were eligible in this study. The median follow-up was 33.1 months, a median PFS of 8.5 months was achieved. Brain metastases (hazard ratio [HR] = 1.582, 95% confidence interval [CI] 1.019- 2.453, P = 0.041) and ≥ 2 metastatic sites (HR = 1.679, 95% CI 1.151–2.450, P = 0.007) were independent prognostic factors for PFS. The most common grade ≥ 3 adverse events were diarrhea (3.8%) and hand-foot syndrome (9.4%). Conclusion The switching mode showed predominant efficacy, which might be a prior therapeutic option over continuing mode in subsequent anti-HER2 therapy for patients with HER2-positive refractory metastatic breast cancer. Trial registration This trial was registered on ClinicalTrials.gov (NCT02362958) on 13/02/2015.