Neutrophil-lymphocyte ratio(NLR) was associated with prognosis and immunomodulatory in patients with pancreatic ductal adenocarcinoma (PDAC).
中性粒细胞-淋巴细胞比值 (NLR) 与胰腺导管腺癌 (PDAC) 患者的预后和免疫调节相关。
- 作者列表："Xiang ZJ","Hu T","Wang Y","Wang H","Xu L","Cui N
:Although the oncological outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) have markedly improved over the past decade, the survival prediction is still challenging. The aim of this study was to investigate the prognostic value of NLR and analyze the relationship of between the NLR and immune cells phenotypes in patients with PDAC. 67 consecutive patients with PDAC were recruited in this study. Life-table estimates of survival time were calculated according to the Kaplan and Meier methodology. The phenotypic T cells subclasses were evaluated by flow cytometry. All the 67 patients in this study were treated with surgical resection and among them, 46 patients received adjuvant chemotherapy. Receiver operating characteristic(ROC) curves analysis were performed to comparison prognostic value of NLR with CA199. We found that the Harrell's Area Under ROC(AUROC) for the NLR to predict overall survival(OS) (0.840; 95% CI, 0.766 to 0.898) was significantly higher than that of CA199 levels. we then stratified all patients into NLR> 2.5(n=42) and NLR ≤2.5(n=25) groups according to the overall survival of patients with PDAC. Survival analysis showed that patients with NLR≤2.5 had significantly favorable OS and progressive free survival(PFS) compared with patients with NLR> 2.5. The CD3+ and CD8+/CD28+ T cell subsets were significantly increased in patients with NLR≤2.5(P<0.05), while the CD8+/CD28- and CD4+/CD25+ cell subsets were significantly decreased in patients with NLR≤2.5 (P <0.05). In conclusion, a high NLR value independently predicts poor survival in patients with PDAC after surgical resection. The NLR was closely related with immune cells phenotypes.
虽然胰腺导管腺癌 (PDAC) 患者的肿瘤学结局在过去十年中显著改善，但生存预测仍然具有挑战性。本研究的目的是探讨 NLR 的预后价值，并分析 NLR 与 PDAC 患者免疫细胞表型之间的关系。本研究连续招募了 67 例 PDAC 患者。根据 Kaplan 和 Meier 方法计算生存时间的寿命表估计值。通过流式细胞术评价表型 T 细胞亚类。本研究 67 例患者均行手术切除，其中 46 例接受辅助化疗。进行受试者工作特征 (ROC) 曲线分析，比较 NLR 与 ca199 的预后价值。我们发现 NLR 预测总生存期 (OS) 的 ROC 下 Harrell 面积 (AUROC) (0.840; 95% CI，0.766 ~ 0.898) 明显高于 CA199 水平。然后我们根据 PDAC 患者的总生存期将所有患者分层为 NLR> 2.5(n = 42) 和 NLR ≤ 2.5(n = 25) 组。生存分析显示，与 NLR> 2.5 的患者相比，NLR ≤ 2.5 的患者具有显著有利的 OS 和无进展生存期 (PFS)。Nlr ≤ 2.5 者 CD3 + 、 CD8 +/CD28 + T 细胞亚群显著升高 (P <0.05),而 CD8 +/CD28-和 CD4 +/CD25 + 细胞亚群在 nlr ≤ 2.5 的患者中显著下降 (P <0.05)。总之，高 NLR 值独立预测 PDAC 患者手术切除后生存率差。NLR 与免疫细胞表型密切相关。
METHODS::Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.
METHODS::Background: SLC6A14 (ATB0,+), a Na+/Cl-coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer.Research design and methods: Here we explored the mechanism of ATB0,+-mediated entry of such liposomes. As ATB0,+ is highly-expressed in pancreatic cancer, we also examined the therapeutic utility of ATB0,+-targeted liposomal drug delivery to treat this cancer.Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB0,+-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB0,+ substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB0,+ occurred via endocytosis with transient endosomal degradation of ATB0,+ protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB0,+-dependent manner.Conclusions: We conclude that ATB0,+ could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.
METHODS:PURPOSE:Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS:We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS:Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS:Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.