Background/Objectives: Sinonasal intestinal-type adenocarcinoma (ITAC) is a rare and aggressive tumor with a lack of specific symptoms, which leads to late diagnosis, and is characterized by frequent local recurrence and low survival rate. The stemness phenotype is one of the main causes leading to tumor proliferation, recurrence, and resistance to standard chemo/radiotherapy.Methods: In this study, genes encoding pluripotency-associated transcription factors, includingKLF4,c-MYC,SOX2,OCT4(Yamanaka factors), andNANOGwere evaluated in malignant and non-malignant tissues of a cohort of 54 patients with ITAC, and their expression was related to patient outcome. The c-MYC, SOX2, and OCT4 levels were then confirmed in immunohistochemistry by adding ALDH1A1 as a factor involved in stemness.Results:KLF4,SOX2, andNANOGbest distinguished cancer tissue from normal tissue with high sensibility and specificity. Low levels ofKLF4,c-MYC, andNANOGand high expressions ofSOX2andOCT4in tumor tissue correlated with poor overall survival (OS) and disease-free survival (DFS), respectively. Through multivariate analysis, type of surgery was found to be a significant prognostic factor along withc-MYCandOCT4. Notably, tumor positivity for c-MYC and ALDH1A1 was associated with longer disease-specific survival, thus suggesting their role as tumor suppressors.Conclusions: Our findings underline the stemness phenotype as a prognostic model for ITAC, supporting the clinical plausibility of Yamanaka factors in sinonasal cancer prediction.
背景/目的：鼻窦肠型腺癌是一种罕见且侵袭性强的肿瘤，缺乏特异性症状，导致诊断延迟，其特点是局部复发频繁且生存率低。干细胞表型是导致肿瘤增殖、复发以及对标准放化疗抵抗的主要原因之一。方法：本研究对54例鼻窦肠型腺癌患者的恶性与非恶性组织中编码多能性相关转录因子的基因进行了评估，包括KLF4、c-MYC、SOX2、OCT4（山中因子）及NANOG，并将其表达与患者预后相关联。随后通过免疫组织化学方法，加入与干细胞特性相关的因子ALDH1A1，进一步验证了c-MYC、SOX2和OCT4的表达水平。结果：KLF4、SOX2和NANOG以高灵敏度和特异性最佳地区分了癌组织与正常组织。肿瘤组织中KLF4、c-MYC和NANOG的低表达以及SOX2和OCT4的高表达分别与较差的总生存期和无病生存期相关。通过多变量分析发现，手术类型与c-MYC和OCT4同为重要的预后因素。值得注意的是，c-MYC和ALDH1A1的肿瘤阳性表达与较长的疾病特异性生存期相关，提示其可能发挥肿瘤抑制因子的作用。结论：我们的研究结果强调了干细胞表型作为鼻窦肠型腺癌预后模型的重要性，支持了山中因子在鼻窦癌预测中的临床可行性。
Clinicopathological Significance of Pluripotent Factors in Sinonasal Intestinal-Type Adenocarcinoma
肿瘤(癌症)患者之家