RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer.
Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer.
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循环脂联素水平较低与结肠癌中 TIL 密度显著增加相关,表明抗肿瘤免疫反应增强。与 TIL 不同,脂联素和 25(OH)D 均不是独立预后因素。
脂肪细胞来源的脂联素可能在宿主对癌症的炎症反应中发挥作用。我们研究了血浆脂联素与结肠癌中TIL(肿瘤浸润淋巴细胞)(TILs)密度以及与维生素D、临床病理特征和患者生存之间的关系。
采用放射免疫分析法对600例接受FOLFOX方案辅助化疗的III期结肠癌患者(NCCTG N0147 [Alliance])的血浆脂联素和25-羟基维生素D [25(OH)D]进行了分析。在组织病理学切片中测定了TIL密度。通过多变量Cox回归校正潜在混杂因素(即体重指数、种族、TILs和N分期)后,评估了其与无病生存期(DFS)、复发时间和总生存期的关联。所有统计学检验均为双侧。
我们发现,与TIL密度低的肿瘤相比,TIL密度高的肿瘤中脂联素水平有统计学显著降低,但25(OH)D没有(中位数 = 6845 vs 8984 ng/mL;P = .04)。在肥胖(体重指数 >30 kg/m 2)与非肥胖患者(中位数 = 6608 vs 12 351 ng/mL;P < .001)、男性与女性(中位数 = 8185 vs 11 567 ng/mL;P < .001)、黑人 vs 白人 vs 亚裔(中位数 = 6412 vs 8847 vs 7858 ng/mL;P < .03)以及淋巴结转移较少者(N1 vs N2:中位数 = 7768 vs 9253 ng/mL;P = .01)中,也观察到脂联素有统计学显著降低。291例(48.5%)患者检测到25(OH)D不足(<30 ng/mL)。在多变量分析中,在调整潜在混杂因素的模型里,脂联素和25(OH)D均与DFS、总生存期或复发时间无统计学显著差异相关。我们发现TILs与预后有统计学显著关联,但在脂联素与TILs对DFS的关联中未观察到这种交互作用。
Adipocyte-derived adiponectin may play a role in the host inflammatory response to cancer. We examined the association of plasma adiponectin with the density of tumor-infiltrating lymphocytes (TILs) in colon cancers and with vitamin D, clinicopathological features, and patient survival.
Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon cancer who received FOLFOX-based adjuvant chemotherapy (NCCTG N0147 [Alliance]). TIL densities were determined in histopathological sections. Associations with disease-free survival (DFS), time to recurrence, and overall survival were evaluated by multivariable Cox regression adjusting for potential confounders (ie, body mass index, race, TILs, and N stage). All statistical tests were 2-sided.
We found a statistically significant reduction in adiponectin, but not 25(OH)D, levels in tumors with high vs low TIL densities (median = 6845 vs 8984 ng/mL; P = .04). A statistically significant reduction in adiponectin was also observed in obese (body mass index >30 kg/m 2 ) vs nonobese patients (median = 6608 vs 12 351 ng/mL; P < .001), in men vs women (median = 8185 vs 11 567 ng/mL; P < .001), in Blacks vs Whites or Asians (median = 6412 vs 8847 vs 7858 ng/mL; P < .03), and in those with fewer lymph node metastases (N1 vs N2: median = 7768 vs 9253 ng/mL; P = .01). Insufficiency of 25(OH)D (<30 ng/mL) was detected in 291 (48.5%) patients. In multivariable analyses, neither adiponectin nor 25(OH)D were associated with a statistically significant difference in DFS, overall survival , or time to recurrence in models adjusted for potential confounders. We found a statistically significant association of TILs with prognosis, yet no such interaction was observed for the association of adiponectin with TILs for DFS.
Lower circulating adiponectin levels were associated with a statistically significant increase in TIL densities in colon cancers, indicating an enhanced antitumor immune response. In contrast to TILs, neither adiponectin nor 25(OH)D was independently prognostic.
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