Hayashi M, Tokuchi Y, Hashimoto T, Hayashi S, Nishida K, Ishikawa Y, Nakagawa K, Tsuchiya S, Okumura S, Tsuchiya E
Laboratory of Cancer Diagnosis and Therapy, Saitama Cancer Center Research Institute, Saitama, Japan.
Anticancer Res. 2001 Jan-Feb;21(1B):535-40.
HIC-1 (hypermethylated in cancer-1) is a candidate tumor suppressor gene, identified in a region of frequent loss of heterozygosity on chromosome 17p13.3, which is telomeric from TP53 and often deleted in surgically resected lung cancers. To determine the significance of HIC-1 in lung cancer, we assessed its expression status and prognostic association in 47 adenocarcinomas and squamous cell carcinomas.
RNA was extracted from tumors and corresponding normal tissues of surgically resected lungs, and the amount of HIC-1 mRNA was determined by means of semi-quantitative reverse transcriptase-polymerase chain reaction.
HIC-1 expression in tumors was less than that in normal lung tissues in 40 of 47 patients (85%), indicating frequent partial silencing. Median tumor/normal lung tissue (T/L) ratios for HIC-1 expression were 0.51 and 0.75 for adenocarcinomas and squamous cell carcinomas, respectively. No significant difference of median T/L ratio was observed between the two histological types, or among clinical stages of the patients. However, the reduced expression of HIC-1 gene in the tumor had a direct link with the clinical outcome: lower T/L ratios (< 0.5) were significantly associated with short survival (P = 0.034), an association also observed in cases restricted to stage I (P = 0.047).
The results suggest that low HIC-1 expression is involved in malignant progression of non-small cell lung cancer.
HIC-1（癌症中高甲基化-1）是一种候选肿瘤抑制基因，在17号染色体短臂13.3区域频繁杂合性缺失区域被鉴定出来，该区域位于TP53基因的端粒侧，在手术切除的肺癌中常发生缺失。为了确定HIC-1在肺癌中的意义，我们评估了其在47例腺癌和鳞状细胞癌中的表达状态及预后相关性。
从手术切除肺的肿瘤组织及相应正常组织中提取RNA，通过半定量逆转录聚合酶链反应测定HIC-1 mRNA的量。
47例患者中有40例（85%）肿瘤组织中HIC-1的表达低于正常肺组织，表明频繁发生部分沉默。腺癌和鳞状细胞癌中HIC-1表达的肿瘤/正常肺组织（T/L）中位数比值分别为0.51和0.75。两种组织学类型之间或患者临床分期之间的T/L中位数比值无显著差异。然而，肿瘤中HIC-1基因表达降低与临床结局直接相关：较低的T/L比值（<0.5）与较短生存期显著相关（P = 0.034），在仅限于I期的病例中也观察到这种相关性（P = 0.047）。
结果表明低HIC-1表达参与非小细胞肺癌的恶性进展。
