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血清 sHLA-G:头颈部鳞状细胞癌治疗和免疫抑制介质的重要诊断生物标志物。

Serum sHLA-G: Significant diagnostic biomarker with respect to therapy and immunosuppressive mediators in Head and Neck Squamous Cell Carcinoma.

机构信息

Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

出版信息

Sci Rep. 2020 Mar 2;10(1):3806. doi: 10.1038/s41598-020-60811-y.

Abstract

Head & Neck Squamous Cell Carcinoma is one of the highest mortality factors in the world due to the lack of potential biomarker for early detection of disease. There is an urgent need for molecular marker involved in disease progression which remains suppressed normally, required for specificity. HLA-G is highly expressed in cancers and creates immune-suppressive microenvironment. Cancerous cells secrete inflammatory cytokines like IL-10,IFN-γ which increase expression of immunosuppressive molecules, such as HLA-G. We evaluated sHLA-G protein level in serum of 120 HNSCC patients at diagnosis and after therapy and compared with 99 individuals by SPR, ELISA and determined its mRNA level by qRT-PCR. sHLA-G was correlated with serum IL-10 and IFN-γ of the patients. Significant elevated levels of sHLA-G were observed in patients (8.25 ± 1.74 ng/µl) than control (6.45 ± 1.31 ng/µl). Levels were declined in (8.09 ± 1.79 ng/µl to 6.64 ± 1.33 ng/µl) patients in response to therapy. sHLA-G levels with tumor burden (8.16 ± 1.91 to 6.63 ± 1.32 ng/µl), node (8.62 ± 1.45 to 6.66 ± 1.26 ng/µl), PDSCC (8.14 ± 0.62 to 5.65 ± 0.27 ng/µl) and oropharynx (7.90 ± 1.24 to 6.10 ± 1.33 ng/µl) showed a positive and significant response to therapy. Findings indicate that sHLA-G can be a potential diagnostic serum protein marker for HNSCC due to its suppressive function and over expression in diseased condition with the influence of cytokines.

摘要

头颈部鳞状细胞癌是世界上死亡率最高的因素之一,因为缺乏疾病早期检测的潜在生物标志物。目前迫切需要一种参与疾病进展的分子标志物,这种标志物通常受到抑制,需要具有特异性。HLA-G 在癌症中高度表达,并创造了免疫抑制的微环境。癌细胞分泌炎症细胞因子,如 IL-10 和 IFN-γ,这些细胞因子增加了免疫抑制分子 HLA-G 的表达。我们通过 SPR、ELISA 评估了 120 例 HNSCC 患者诊断时和治疗后的血清 sHLA-G 蛋白水平,并与 99 例个体进行了比较,并通过 qRT-PCR 测定了其 mRNA 水平。sHLA-G 与患者的血清 IL-10 和 IFN-γ相关。与对照组(6.45±1.31ng/µl)相比,患者的 sHLA-G 水平显著升高(8.25±1.74ng/µl)。治疗后,患者的 sHLA-G 水平从(8.09±1.79ng/µl 至 6.64±1.33ng/µl)下降。sHLA-G 水平与肿瘤负荷(8.16±1.91 至 6.63±1.32ng/µl)、淋巴结(8.62±1.45 至 6.66±1.26ng/µl)、局部晚期(8.14±0.62 至 5.65±0.27ng/µl)和口咽(7.90±1.24 至 6.10±1.33ng/µl)对治疗有积极且显著的反应。这些发现表明,由于 sHLA-G 在疾病状态下具有抑制功能和过表达,并受到细胞因子的影响,因此 sHLA-G 可以成为 HNSCC 的潜在诊断血清蛋白标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aede/7052243/2c49d23c77bb/41598_2020_60811_Fig1_HTML.jpg

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