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Abstract：
Despite its histological resemblance to colorectal adenocarcinoma, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITAC). The present study investigated the possible role and clinical value of microRNA (miR)-let-7a, a head and neck squamous cell carcinoma-related miR, in a well-characterized and homogeneous cohort of patients with ethmoidal ITAC associated with occupational exposure, treated by primary surgery. miR-let-7a expression levels were analyzed in 23 pairs of ethmoidal ITAC and adjacent normal formalin-fixed paraffin-embedded tissues by reverse transcription-quantitative PCR. The expression was evaluated in tumor and healthy tissues according to: Tumor grade (G) of differentiation and extension, and pTNM stage, and presence/absence of recurrence. Comparisons within and between groups were performed using two-tailed Student\'s paired t-test and one-way ANOVA with Tukey\'s post hoc test. P<0.05 was considered to indicate a statistically significant difference. miR-let-7a expression in ethmoidal ITAC tissues was significantly lower than that in adjacent normal tissues (P<0.05; mean expression level ± SD, 1.452707±1.4367189 vs. 4.094017±2.7465375). miR expression varied with pT stage. miR-let-7a was downregulated (P<0.05) in advanced stages (pT3-pT4) compared with earlier stages (pT1-pT2). Furthermore, downregulation of miR-let-7a in ITAC was associated with poorly-differentiated (G3) cancer (P<0.05). No other associations were observed between miR-let-7a expression and the other clinicopathological parameters, including disease-free survival. In conclusion, downregulation of miR-let-7a in ITAC was associated with advanced-stage (pT3 and pT4) and poorly-differentiated (G3) disease, suggesting that the mutation of this gene, combined with additional genetic events, could serve a role in ITAC pathogenesis.
摘要：
尽管它在组织学上与结直肠腺癌相似，关于肠型鼻窦腺癌(ITAC)发病机制涉及的分子事件的信息很少.本研究探讨了微小RNA（miR）-let-7a的可能作用和临床价值，头颈部鳞状细胞癌相关的miR，在与职业暴露相关的筛骨ITAC患者中，通过初级手术治疗。通过逆转录-定量PCR分析了23对筛检ITAC和邻近的正常福尔马林固定石蜡包埋组织中的miR-let-7a表达水平。根据以下方法评估肿瘤和健康组织中的表达：分化和扩展的肿瘤分级（G），和pTNM阶段，和复发的存在/不存在。使用双尾学生配对t检验和单因素方差分析和Tukey事后检验进行组内和组间比较。P<0.05被认为表示统计学上的显著差异。miR-let-7a在筛骨ITAC组织中的表达显著低于癌旁正常组织(P<0.05;平均表达水平±SD,1.452707±1.4367189vs.4.094017±2.7465375)。miR表达随pT分期而变化。与早期阶段（pT1-pT2）相比，miR-let-7a在晚期阶段（pT3-pT4）下调（P<0.05）。此外，miR-let-7a在ITAC中的下调与低分化（G3）癌症相关（P<0.05）。在miR-let-7a表达和其他临床病理参数之间没有观察到其他关联，包括无病生存。总之,ITAC中miR-let-7a的下调与晚期（pT3和pT4）和低分化（G3）疾病有关，表明这个基因的突变，再加上额外的遗传事件，可能在ITAC发病机制中发挥作用。
