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TGM-3 在组织和血清中的表达可能是接受放化疗的口腔鳞状细胞癌患者的预后标志物。

Tissue and serum expression of TGM-3 may be prognostic marker in patients of oral squamous cell carcinoma undergoing chemo-radiotherapy.

机构信息

Department of Radiotherapy, King George's Medical University Lucknow, Uttar Pradesh, India.

Department of Pathology, King George's Medical University Lucknow, Uttar Pradesh, India.

出版信息

PLoS One. 2018 Jun 28;13(6):e0199665. doi: 10.1371/journal.pone.0199665. eCollection 2018.

Abstract

Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors aimed to establish radioresistant OSCC cell lines to identify genes with altered expression in response to radioresistance. The development of OSCC is a multistep carcinogenic process that includes activation of several oncogenes and inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and contributes to carcinogenesis process. The aim of this study was to estimate serum and tissue expression of TGM-3 and its correlation with clinico-pathological factors and overall survival in patients of OSCC undergoing chemo-radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of 96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry (IHC) by using antibody against TGM-3 and serum level was estimated by ELISA method. mRNA expression was determined by using Real-Time PCR. Patients were followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was cytoplasmic and nuclear staining expressed in keratinized layer, stratum granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in pre chemo-radiotherapy OSCC cases were 1304.83±573.55, post chemo-radiotherapy samples were 1530.64±669.33 and controls were 1869.16±1377.36, but difference was significant in pre chemo-radiotherapy samples as compared to controls (p<0.018). This finding was also confirmed by real- time PCR analysis in which down regulation (-7.92 fold change) of TGM-3 in OSCC as compared to controls. TGM-3 expression was significantly associated with response to chemo-radiotherapy treatment (p<0.007) and overall survival (p<0.015). Patents having higher level of TGM-3 expression have good response to chemo-radiotherapy and also have better overall survival. TGM-3 may serve as a candidate biomarker for responsiveness to chemo-radiotherapy treatment in OSCC patients.

摘要

放射抵抗性是口腔鳞状细胞癌(OSCC)治疗结果的主要决定因素之一,但预测难度较大。一些作者旨在建立放射抵抗性 OSCC 细胞系,以鉴定对放射抵抗性有反应的表达改变的基因。OSCC 的发展是一个多步骤的致癌过程,包括几个癌基因的激活和肿瘤抑制基因的失活。TGM-3 是一种肿瘤抑制基因,有助于致癌过程。本研究旨在评估血清和组织中 TGM-3 的表达及其与接受化疗-放疗的 OSCC 患者的临床病理因素和总生存率的相关性。使用针对 TGM-3 的抗体通过免疫组织化学(IHC)观察 96 例 OSCC 患者的福尔马林固定组织活检中的组织表达,并通过 ELISA 法估计血清水平。使用 Real-Time PCR 确定 mRNA 表达。对患者进行了 2 年的化疗-放疗反应随访。在 OSCC 中,76.70%的病例和对照组中 90.62%的病例 TGM-3 IHC 表达阳性。TGM-3 表达为细胞质和核染色,在对照组和肿瘤细胞中表达在角质层、颗粒层和棘层。化疗前 OSCC 病例的平均血清 TGM-3 为 1304.83±573.55,化疗后样本为 1530.64±669.33,对照组为 1869.16±1377.36,但化疗前样本与对照组相比差异有统计学意义(p<0.018)。这一发现也通过实时 PCR 分析得到证实,其中 OSCC 中 TGM-3 的下调(-7.92 倍变化)与对照组相比。TGM-3 表达与化疗-放疗治疗反应(p<0.007)和总生存率(p<0.015)显著相关。TGM-3 表达较高的患者对化疗-放疗有较好的反应,总生存率也较好。TGM-3 可能成为 OSCC 患者对化疗-放疗治疗反应的候选生物标志物。

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