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Purpose: Programmed cell death ligand 1 (PDL1) has the predictive and prognostic value in a great deal of cancers. This study aims to explore the expression of PDL1 in stage III breast cancer (BC) and its correlation with clinical outcome. Methods: The protein expression of PDL1 in tumor tissues was determined by immunohistochemistry (IHC). The correlations between PDL1 and clinicopathological variables were performed by χ²-tests or Fisher's exact tests. The Cox proportional hazards model was used for univariate and multivariate analysis of the potential prognostic factors. Survival curves were estimated based on Kaplan-Meier analyses, and Log Rank test was used to contrast factors influencing the survival outcome. Results: On the basis of the semiquantitative scoring method for PDL1 expression, the patients were divided into low PDL1 expression group (109 cases) and high PDL1 expression group (107 cases). PDL1 expression was correlated with positive lymph nodes, positive axillary lymph nodes, postoperative radiotherapy, and CK5/6 expression (P < 0.05). The PDL1 expression in tumor tissues was discovered to be a potential prognostic risk factor with the disease-free survival (DFS) and overall survival (OS) for stage III BC. Moreover, patients with high PDL1 expression showed longer lifetime (DFS and OS) compared to those with low PDL1 expression in total patient population (P < 0.05). Moreover, the nomogram showed that the prediction line is in good agreement with the reference line for postoperative 1-, 3-, and 5-year lifetime. The DCA curve showed that the 3- and 5-year lifetime by nomogram had so much better divination of the clinical application than only by PDL1. Conclusion: PDL1 is a latent prognostic factor in stage III BC and is closely related to some clinicopathological features. PDL1 expression in tumor tissues is significantly associated with better lifetime rate in stage III BC.
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BACKGROUND: Propofol is a common sedative-hypnotic drug traditionally used for inducing and maintaining general anesthesia. Recent studies have drawn attention to the nonanesthetic effects of propofol, but the potential mechanism by which propofol suppresses non-small-cell lung cancer (NSCLC) progression has not been fully elucidated. METHODS: For the in vitro experiments, we used propofol (0, 2, 5, and 10 µg/mL) to treat A549 cells for 1, 4, and 12 hours and Cell Counting Kit-8 (CCK-8) to detect proliferation. Apoptosis was measured with flow cytometry. We also transfected A549 cells with an microribonucleic acid-21 (miR-21) mimic or negative control ribonucleic acid (RNA) duplex and phosphatase and tensin homolog, deleted on chromosome 10 (PTEN) small interfering ribonucleic acid (siRNA) or negative control. PTEN, phosphorylated protein kinase B (pAKT), and protein kinase B (AKT) expression were detected using Western blotting, whereas miR-21 expression was examined by real-time polymerase chain reaction (RT-PCR). In vivo, nude mice were given injections of A549 cells to grow xenograft tumors; 8 days later, the mice were intraperitoneally injected with propofol (35 mg/kg) or soybean oil. Tumors were then collected from mice and analyzed by immunohistochemistry and Western blotting. RESULTS: Propofol inhibited growth (1 hour, P = .001; 4 hours, P ≤ .0001; 12 hours, P = .0004) and miR-21 expression (P ≤ .0001) and induced apoptosis (1 hour, P = .0022; 4 hours, P = .0005; 12 hours, P ≤ .0001) in A549 cells in a time and concentration-dependent manner. MiR-21 mimic and PTEN siRNA transfection antagonized the suppressive effects of propofol on A549 cells by decreasing PTEN protein expression (mean differences [MD] [95% confidence interval {CI}], -0.51 [-0.86 to 0.16], P = .0058; MD [95% CI], 0.81 [0.07-1.55], P = .0349, respectively), resulting in an increase in pAKT levels (MD [95% CI] = -0.82 [-1.46 to -0.18], P = .0133) following propofol exposure. In vivo, propofol treatment reduced NSCLC tumor growth (MD [95% CI] = -109.47 [-167.03 to -51.91], P ≤ .0001) and promoted apoptosis (MD [95% CI] = 38.53 [11.69-65.36], P = .0093). CONCLUSIONS: Our study indicated that propofol inhibited A549 cell growth, accelerated apoptosis via the miR-21/PTEN/AKT pathway in vitro, suppressed NSCLC tumor cell growth, and promoted apoptosis in vivo. Our findings provide new implications for propofol in cancer therapy and indicate that propofol is extremely advantageous in surgical treatment.