Serum sHLA-G: Significant diagnostic biomarker with respect to therapy and immunosuppressive mediators in Head and Neck Squamous Cell Carcinoma
Serum sHLA-G: Significant diagnostic biomarker with respect to therapy and immunosuppressive mediators in Head and Neck Squamous Cell Carcinoma
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DOI：
10.1038/s41598-020-60811-y
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发表时间：
2020-03-02
影响因子：
4.6
通讯作者：
Dey, Sharmistha
中科院分区：
文献类型：
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作者：
Agnihotri, Vertica;Gupta, Abhishek;Dey, Sharmistha
由于缺乏早期发现疾病的潜在生物标志物，头颈部鳞状细胞癌是世界上死亡率最高的因素之一。目前迫切需要一种参与疾病进展的分子标记物，这种分子标记物在正常情况下仍被抑制，需要特异性。HLA-G在癌症中高表达并产生免疫抑制微环境。癌细胞分泌炎性细胞因子，如IL-10， ifn - γ，增加免疫抑制分子的表达，如HLA-G。我们对120例HNSCC患者在诊断和治疗后的血清sHLA-G蛋白水平进行了评估，并与99例患者进行了SPR、ELISA和qRT-PCR的比较。sHLA-G与患者血清IL-10、ifn - γ相关。患者sHLA-G水平（8.25 +/- 1.74 ng/mu l）显著高于对照组（6.45 +/- 1.31 ng/mu l）。治疗后，患者的水平下降（8.09 +/- 1.79 ng/ μ l至6.64 +/- 1.33 ng/ μ l）。sHLA-G水平在肿瘤负荷（8.16 +/- 1.91 ~ 6.63 +/- 1.32 ng/ μ l）、淋巴结（8.62 +/- 1.45 ~ 6.66 +/- 1.26 ng/ μ l）、PDSCC （8.14 +/- 0.62 ~ 5.65 +/- 0.27 ng/ μ l）和口咽部（7.90 +/- 1.24 ~ 6.10 +/- 1.33 ng/ μ l）中均对治疗有积极而显著的反应。结果表明，sHLA-G具有抑制功能，在细胞因子的影响下在病变状态下过表达，可作为诊断HNSCC的潜在血清蛋白标志物。
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-gamma 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-gamma of the patients. Significant elevated levels of sHLA-G were observed in patients (8.25 +/- 1.74 ng/mu l) than control (6.45 +/- 1.31 ng/mu l). Levels were declined in (8.09 +/- 1.79 ng/mu l to 6.64 +/- 1.33 ng/mu l) patients in response to therapy. sHLA-G levels with tumor burden (8.16 +/- 1.91 to 6.63 +/- 1.32 ng/mu l), node (8.62 +/- 1.45 to 6.66 +/- 1.26 ng/mu l), PDSCC (8.14 +/- 0.62 to 5.65 +/- 0.27 ng/mu l) and oropharynx (7.90 +/- 1.24 to 6.10 +/- 1.33 ng/mu l) 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.