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IL-12Rβ2与IL-23R表达对喉癌患者预后的联合影响

Combined Effect of IL-12Rβ2 and IL-23R Expression on Prognosis of Patients with Laryngeal Cancer.

作者信息

Tao Ye, Tao Tianchang, Gross Neil, Peng Xuyun, Li Ying, Huang Zhigang, Liu Limei, Li Guojun, Chen Xiaohong, Yang Jianming

机构信息

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Beijing Tongren Eye Center, Beijing Tongren hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.

出版信息

Cell Physiol Biochem. 2018;50(3):1041-1054. doi: 10.1159/000494515. Epub 2018 Oct 24.

Abstract

BACKGROUND/AIMS: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC).

METHODS

The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival.

RESULTS

LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4).

CONCLUSION

IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.

摘要

背景/目的:本研究旨在从病理学角度阐明白细胞介素-12受体(IL-12R)β2和白细胞介素-23受体(IL-23R)在肿瘤微环境中的肿瘤细胞和肿瘤浸润淋巴细胞(TIL)中的表达作用,并确定它们对喉癌(LC)预后的联合影响。

方法

通过免疫组织化学(IHC)检测61例LC患者匹配的LC组织和正常喉组织样本中IL-12Rβ2和IL-23R的肿瘤细胞表达评分和TIL阳性率。我们采用线性回归模型分析肿瘤细胞中IL-12Rβ2和IL-23R表达与TIL比率之间的相关性。采用Kaplan-Meier对数秩检验和Cox回归风险比分析生存率。

结果

LC肿瘤细胞中IL-12Rβ2表达和TIL比率高于IL-23R表达和TIL比率。在LC组织中,尤其是高分化LC中,IL-12Rβ2和IL-23R表达与TIL比率之间存在显著相关性。此外,肿瘤细胞IL-12Rβ2高表达或IL-23R低表达的生存率分别优于相应的低表达或高表达。IL-12Rβ2比率和IL-23R比率也有类似结果。最后,在所有基因表达组合组中,IL-12Rβ2高表达且IL-23R低表达的患者预后最佳(风险比,0.1;95%可信区间,0.0-0.8)。同样,IL-12Rβ2高表达且IL-23R TIL低阳性率的患者生存率最高(风险比,0.1;95%可信区间,0.0-0.4)。

结论

IL-12Rβ2和IL-23R在肿瘤细胞和TIL之间建立了一种稳态,这种稳态影响预后。虽然IL-12Rβ2和IL-23R的表观遗传免疫编辑的内在机制尚不清楚,但需要更多更大规模的功能研究来验证。

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