通过实时逆转录聚合酶链反应对头颈部癌中多药耐药mdr1基因表达进行定量分析。

Quantitative analysis of multidrug-resistance mdr1 gene expression in head and neck cancer by real-time RT-PCR.

作者信息

Tseng Ching-Ping, Cheng Ann-Joy, Chang Joseph Tung-Chieh, Tseng Chin-Hsiao, Wang Hung-Ming, Liao Chun-Ta, Chen I-How, Tseng Kelvin Chingchung

机构信息

School of Medical Technology, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.

出版信息

Jpn J Cancer Res. 2002 Nov;93(11):1230-6. doi: 10.1111/j.1349-7006.2002.tb01228.x.

DOI:10.1111/j.1349-7006.2002.tb01228.x

PMID:12460464

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5926900/

Abstract

Progression of head and neck cancer is always associated with changes of gene expression profile. In this study, we characterized the expression of multidrug-resistance mdr1 gene, which may play a role in tumorigenesis and multidrug resistance in head and neck cancer. A TaqMan one-step RT-PCR with a linear range for quantification across at least a 5 log scale of concentration of mdr1 mRNA was designed to determine the level of mdr1 expression in 50 pairs of normal vs. malignant head and neck tissues. Both the absolute level of mdr1 mRNA in tumor (T) and the relative mdr1 expression between tumor and its normal counterpart (T/N) were measured and their associations with several clinical variables were analyzed. Among the clinical variables analyzed, only the clinical stage of tumor was found to be associated with mdr1 expression. The distribution of clinical stages differed significantly (P<0.01) among the 27 specimens that had a T/N>1, with 59.3%, 22.2%, 14.8% and 3.7% in stage IV, III, II, and I, respectively. In addition, 76% of stage IV and 75% of stage III tumors had a T/N>1 compared to 25% of stage II and 20% of stage I tumors (P=0.004). Multivariate logistic regression analysis also indicated a significant difference of mdr1 expression between the early (I and II) and advanced (III and IV) stages tumors. The adjusted odds ratios (95% confidence intervals) were 1.477 (1.084 - 2.012) and 1.001 (1.000-1.002) for T/N (P<0.05) and T (P<0.05) treated as continuous variables, and 15.521 (3.414-70.550) and 5.074 (1.154-22.311) for T/N (P<0.001) and T (P<0.05) treated as binary variables, respectively. Taken together, the data presented here indicated that real-time RT-PCR provides a quantitative way to monitor mdr1 gene expression. The differential expression of mdr1 between early and advanced stages of head and neck cancer may shed light on the process of tumorigenicity and offer clues to the planning of new treatments.

摘要

头颈癌的进展总是与基因表达谱的变化相关。在本研究中，我们对多药耐药mdr1基因的表达进行了表征，该基因可能在头颈癌的肿瘤发生和多药耐药中发挥作用。设计了一种TaqMan一步法RT-PCR，其线性定量范围跨越至少5个对数级的mdr1 mRNA浓度，以确定50对正常与恶性头颈组织中mdr1的表达水平。测量了肿瘤中mdr1 mRNA的绝对水平以及肿瘤与其正常对应组织之间的mdr1相对表达（T/N），并分析了它们与几个临床变量的关联。在分析的临床变量中，仅发现肿瘤的临床分期与mdr1表达相关。在27个T/N>1的标本中，临床分期分布差异显著（P<0.01），IV期、III期、II期和I期分别为59.3%、22.2%、14.8%和3.7%。此外，IV期肿瘤的76%和III期肿瘤的75%的T/N>1，而II期肿瘤的25%和I期肿瘤的20%的T/N>1（P=0.004）。多变量逻辑回归分析也表明，早期（I期和II期）和晚期（III期和IV期）肿瘤之间mdr1表达存在显著差异。将T/N（P<0.05）和T（P<0.05）作为连续变量处理时，调整后的优势比（95%置信区间）分别为1.477（1.084 - 2.012）和1.001（1.000 - 1.002）；将T/N（P<0.001）和T（P<0.05）作为二元变量处理时，调整后的优势比分别为十五点五二一（3.414 - 70.550）和五点零七四（1.154 - 22.311）。综上所述，此处呈现的数据表明实时RT-PCR提供了一种定量监测mdr1基因表达的方法。头颈癌早期和晚期之间mdr1的差异表达可能有助于揭示肿瘤发生过程，并为新治疗方案的规划提供线索。