PDF(Pubmed)
Abstract：
BACKGROUND: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry.
METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 μm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher\'s exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis.
RESULTS: H-score of 90 in nucleus was appropriate cutoff value for \'High PSMD1 expression\' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively).
CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.
METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 μm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher\'s exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis.
RESULTS: H-score of 90 in nucleus was appropriate cutoff value for \'High PSMD1 expression\' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively).
CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.
摘要：
背景：尽管头颈部癌有不同的基因突变，这种癌症的化疗结果几十年来没有改善。选择口咽肿瘤的预后因素和治疗靶点是建立精准医疗的当务之急。最近的研究已经确定PSMD1是几种癌症的潜在预后标志物。我们旨在使用免疫组织化学评估PSMD1表达在口咽鳞状细胞癌（OPSCC）患者中的预后意义。
方法：我们研究了2008年4月至2017年8月在首尔国立大学Bundang医院接受手术的64例OPSCC组织。对p16和PSMD1的组织微阵列(TMA)切片(4μm)进行免疫染色分析。H分数,从每个原子核计算出从0到300的标度，细胞质，和细胞表达。临床病理数据与卡方检验比较，费希尔的精确检验，t检验,和逻辑回归。到2021年的生存数据来自韩国国家统计局。使用Kaplan-Meier方法和cox回归模型进行疾病特异性生存（DSS）分析。
结果：细胞核中的H评分90是OPSCC中“高PSMD1表达”的适当截止值。低PSMD1组（42/52，80.8％）的扁桃体位置高于高PSMD1组（4/12，33.3％；P=.002）。低PSMD1组（45/52，86.5％）的早期肿瘤发生率高于高PSMD1组（6/12，50％；P=0.005）。低PSMD1组HPV阳性（43/52，82.7%）高于高PSMD1组（5/12，41.7%；P=0.016）。与PSMD1低表达患者相比，PSMD1高表达患者的DSS较差（对数秩检验P=.006）。在多变量分析中，PSMD1表达式，病理性T分期,样本年龄与DSS相关（分别为P=.011，P=.025，P=.029）。
结论：在我们的研究中，我们将PSMD1确定为口咽鳞癌的阴性预后因素，表明其作为靶向治疗的靶标的潜力，并为未来的药物重新定位体外研究铺平了道路。
方法：我们研究了2008年4月至2017年8月在首尔国立大学Bundang医院接受手术的64例OPSCC组织。对p16和PSMD1的组织微阵列(TMA)切片(4μm)进行免疫染色分析。H分数,从每个原子核计算出从0到300的标度，细胞质，和细胞表达。临床病理数据与卡方检验比较，费希尔的精确检验，t检验,和逻辑回归。到2021年的生存数据来自韩国国家统计局。使用Kaplan-Meier方法和cox回归模型进行疾病特异性生存（DSS）分析。
结果：细胞核中的H评分90是OPSCC中“高PSMD1表达”的适当截止值。低PSMD1组（42/52，80.8％）的扁桃体位置高于高PSMD1组（4/12，33.3％；P=.002）。低PSMD1组（45/52，86.5％）的早期肿瘤发生率高于高PSMD1组（6/12，50％；P=0.005）。低PSMD1组HPV阳性（43/52，82.7%）高于高PSMD1组（5/12，41.7%；P=0.016）。与PSMD1低表达患者相比，PSMD1高表达患者的DSS较差（对数秩检验P=.006）。在多变量分析中，PSMD1表达式，病理性T分期,样本年龄与DSS相关（分别为P=.011，P=.025，P=.029）。
结论：在我们的研究中，我们将PSMD1确定为口咽鳞癌的阴性预后因素，表明其作为靶向治疗的靶标的潜力，并为未来的药物重新定位体外研究铺平了道路。
