a Developmental Toxicology Laboratory, System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.
b School of Dental Sciences, Department of Biochemistry, Babu Banarsi Das University , Lucknow , India.
Biomarkers. 2019 Sep;24(6):574-583. doi: 10.1080/1354750X.2019.1609090. Epub 2019 Jun 4.
To develop peripheral blood mRNA expression profiles of drug metabolizing enzymes (DMEs) as a surrogate to monitor tobacco induced head and neck squamous cell carcinoma (HNSCC), attempts were made to investigate (i) similarities in alterations with the cancer marker genes in biopsy samples and (ii) if alterations similar to that seen in biopsy samples are reflected in peripheral blood. Total RNA from eight soft gingival tissues and eight biopsy samples of HNSCC patients and total DNA and RNA from blood of healthy controls ( = 150) and HNSCC patients ( = 150) was processed for expression and genotyping studies. Blood from patients receiving chemo-radiotherapy was processed for follow-up study. qRT-PCR revealed significant increase in mRNA expression of DMEs in biopsy and blood samples of HNSCC patients when compared to controls. Similar alterations were observed in cancer marker genes in these samples. Patients with variant genotypes of DMEs showed greater magnitude of alterations in mRNA expression when compared to wild type controls. Responders of chemo-radiotherapy showed significant decline in induction of mRNA expression of DMEs and cancer marker genes The data suggest that peripheral blood expression profiles could be used to monitor tobacco-induced HNSCC as well as the treatment response.
为了开发外周血 mRNA 表达谱作为监测烟草诱导的头颈部鳞状细胞癌(HNSCC)的替代物,尝试研究了(i)活检样本中与癌症标志物基因的改变的相似性,以及(ii)外周血中是否反映了与活检样本中相似的改变。 从 8 例软牙龈组织和 8 例 HNSCC 患者的活检样本中提取总 RNA,从 150 例健康对照者和 150 例 HNSCC 患者的血液中提取总 DNA 和 RNA,进行表达和基因分型研究。对接受化疗和放疗的患者的血液进行了随访研究。 qRT-PCR 显示,与对照组相比,HNSCC 患者的活检和血液样本中 DMEs 的 mRNA 表达显著增加。在这些样本中,癌症标志物基因也观察到了类似的改变。与野生型对照相比,DMEs 变异基因型患者的 mRNA 表达改变幅度更大。化疗和放疗的应答者表现出 DMEs 和癌症标志物基因的 mRNA 表达诱导的显著下降。 数据表明,外周血表达谱可用于监测烟草诱导的 HNSCC 以及治疗反应。