Dihlmann Susanne, Tao Sha, Echterdiek Fabian, Herpel Esther, Jansen Lina, Chang-Claude Jenny, Brenner Hermann, Hoffmeister Michael, Kloor Matthias
Department of Vascular and Endovascular Surgery, University of Heidelberg, Heidelberg, Germany.
Int J Cancer. 2014 Nov 15;135(10):2387-96. doi: 10.1002/ijc.28891. Epub 2014 Apr 28.
Functional studies on colorectal cancer cells indicated a protective role of the interferon-inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5-year follow-up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers. Samples from 62 patients were excluded because of missing follow-up information or due to neo-adjuvant therapy before tissue sampling. Out of the remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in cancer cells when compared to epithelial cells of their normal counterpart. Thirty-eight patients (9.18%) had completely lost AIM2 expression in tumor cells. After adjustment for sex, age, cancer stage, tumor site, tumor grade and chemotherapy, complete lack of AIM2 expression was associated with an up to 3-fold increase in overall mortality (HR=2.40; 95% CI=1.44-3.99) and disease specific mortality (HR=3.14; 95% CI=1.75-5.65) in comparison to AIM2-positive tumor samples. Our results demonstrate that lack of AIM2 expression is closely associated with poor outcome in colorectal cancer. The data thus strongly substantiate a protective role of AIM2 against progression of colorectal tumors. Further studies are required to assess whether lack of AIM2 expression may be used as a biomarker for the identification of colorectal cancer patients with poor prognosis.
对结肠直肠癌细胞的功能研究表明，干扰素诱导的双链DNA传感器黑色素瘤2缺失（AIM2）在癌症进展中具有保护作用。鉴于先前在一部分结肠直肠癌中检测到高突变率和AIM2表达缺失，我们在此研究了肿瘤细胞中AIM2表达与患者预后（5年随访）的关联。由两名独立观察者对476对匹配的组织样本（结肠直肠肿瘤和相邻的正常结肠上皮）进行组织微阵列分析。由于缺少随访信息或在组织采样前接受新辅助治疗，排除了62例患者的样本。在其余414对组织样本中，与正常对应上皮细胞相比，279对（67.4%）癌细胞中的AIM2表达降低。38例患者（9.18%）肿瘤细胞中完全丧失AIM2表达。在调整性别、年龄、癌症分期、肿瘤部位、肿瘤分级和化疗因素后，与AIM2阳性肿瘤样本相比，AIM2表达完全缺失与总死亡率（HR=2.40；95%CI=1.44-3.99）和疾病特异性死亡率（HR=3.14；95%CI=1.75-5.65）升高高达3倍相关。我们的结果表明，AIM2表达缺失与结肠直肠癌的不良预后密切相关。因此，这些数据有力地证实了AIM2对结肠直肠肿瘤进展具有保护作用。需要进一步研究评估AIM2表达缺失是否可作为识别预后不良的结肠直肠癌患者的生物标志物。
