Schulze Arik Bernard, Kuntze Anna, Schmidt Lars Henning, Mohr Michael, Marra Alessandro, Hillejan Ludger, Schulz Christian, Görlich Dennis, Hartmann Wolfgang, Bleckmann Annalen, Evers Georg
Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany.
West German Cancer Center, University Hospital Muenster, 48149 Muenster, Germany.
Cancers (Basel). 2022 Mar 9;14(6):1395. doi: 10.3390/cancers14061395.
Via immunohistochemistry (IHC) on tissue micro arrays (TMA) clinical and prognostic impact of p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein expression was evaluated in 252 NSCLC patients. Confirmatory, gene expression database. mRNA levels of NT5DC2 were studied in 1925 NSCLC patients. High protein expression of NT5DC2 resulted in reduced median overall survival (OS) of patients with stage I-III adenocarcinoma (ADC) (Log Rank p = 0.026, HR 2.04 (1.08−3.87)), but not in squamous cell carcinoma (SCC) (p = 0.514, HR 0.87 (0.57−1.33)). Findings on OS were reproduced via gene expression analysis in ADC (p < 0.001, HR 1.64 (1.30−2.08)) and SCC (p = 0.217, HR 0.86 (0.68−1.09)). Yet, NT5DC2 mRNA levels were higher in SCC compared to ADC (p < 0.001) and in pN2 tumors compared to pN0/1 tumors (p = 0.001). Likewise, NT5DC2 protein expression associated with high-grade SCC. Moreover, NT5DC2 expression was positively correlated with p53 protein (p = 0.018) and TP53 gene expression (p < 0.001) and its survival effect was p53 dependent. While p53 expression was negatively associated with the presence of CD34+ cancer associated fibroblasts (CAFs), NT5DC2 expression insignificantly tended to higher levels of SMA+ CAFs (p = 0.065).
通过组织微阵列（TMA）上的免疫组织化学（IHC），在252例非小细胞肺癌（NSCLC）患者中评估了p53协同发挥作用的含5'-核苷酸酶结构域蛋白2（NT5DC2）蛋白表达的临床和预后影响。进行了验证性基因表达数据库研究。在1925例NSCLC患者中研究了NT5DC2的mRNA水平。NT5DC2的高蛋白表达导致I-III期腺癌（ADC）患者的中位总生存期（OS）缩短（对数秩检验p = 0.026，风险比[HR] 2.04 [1.08 - 3.87]），但在鳞状细胞癌（SCC）中未出现这种情况（p = 0.514，HR 0.87 [0.57 - 1.33]）。通过基因表达分析在ADC（p < 0.001，HR 1.64 [1.30 - 2.08]）和SCC（p = 0.217，HR 0.86 [0.68 - 1.09]）中再现了关于OS的研究结果。然而，与ADC相比，SCC中的NT5DC2 mRNA水平更高（p < 0.001），与pN0/1肿瘤相比，pN2肿瘤中的NT5DC2 mRNA水平更高（p = 0.001）。同样，NT5DC2蛋白表达与高级别SCC相关。此外，NT5DC2表达与p53蛋白呈正相关（p = 0.018），与TP53基因表达呈正相关（p < 0.001），其生存效应依赖于p53。虽然p53表达与CD34 + 癌症相关成纤维细胞（CAF）的存在呈负相关，但NT5DC2表达与SMA + CAF的较高水平无显著相关性（p = 0.065）。
