Abstract：
BACKGROUND: Overexpression of human epididymis protein 4 (HE4) was previously described in idiopathic pulmonary fibrosis (IPF), but whether serum HE4 can be considered as a potential biomarker in connective tissue disease-associated interstitial lung disease (CTD-ILD) with usual interstitial pneumonia (UIP) pattern was still unknown.
METHODS: A total of 55 CTD-ILD patients with UIP pattern (UIP-CTD) and 52 healthy controls were enrolled in this study. The serum levels of HE4 and Krebs von den Lungen-6 (KL-6) were evaluated in both cohorts. In addition, immunohistochemistry analysis for HE4 was performed on the lung sections of 6 patients with rheumatoid arthritis-associated UIP (UIP-RA) and 6 patients with early-stage lung cancer as normal control.
RESULTS: The levels of serum HE4 and KL-6 were higher in patients with UIP-CTD than in healthy controls (292.3 pmol/L versus 79.5 pmol/L for HE4, p < 0.001; 1091.0 IU/mL versus 171.5 IU/mL for KL-6, p < 0.001). Significant correlations between serum HE4 levels and percentpredicted forced vital capacity (FVC%) (r = -0.425, p = 0.004), percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r = -0.447, p = 0.003), and Gender-Age-Physiology (GAP) index (r = 0.494, p < 0.001) were observed in UIP-CTD patients. In immunohistochemistry analysis, elevated expression of HE4 in bronchiolar epithelium and mesenchyme was observed in patients with UIP-RA compared with controls. The serum levels of HE4 (≥277.5 pmol/L) and GAP index were related to an increased risk of mortality (HR = 3.884, p = 0.034; HR = 1.480, p = 0.028, respectively).
CONCLUSIONS: The expression of HE4 in serum and lung specimens was significantly elevated in UIP-CTD patients. Moreover, serum HE4 may be utilized as a biomarker to evaluate the severity of disease and predict the prognosis of UIP-CTD patients.
METHODS: A total of 55 CTD-ILD patients with UIP pattern (UIP-CTD) and 52 healthy controls were enrolled in this study. The serum levels of HE4 and Krebs von den Lungen-6 (KL-6) were evaluated in both cohorts. In addition, immunohistochemistry analysis for HE4 was performed on the lung sections of 6 patients with rheumatoid arthritis-associated UIP (UIP-RA) and 6 patients with early-stage lung cancer as normal control.
RESULTS: The levels of serum HE4 and KL-6 were higher in patients with UIP-CTD than in healthy controls (292.3 pmol/L versus 79.5 pmol/L for HE4, p < 0.001; 1091.0 IU/mL versus 171.5 IU/mL for KL-6, p < 0.001). Significant correlations between serum HE4 levels and percentpredicted forced vital capacity (FVC%) (r = -0.425, p = 0.004), percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r = -0.447, p = 0.003), and Gender-Age-Physiology (GAP) index (r = 0.494, p < 0.001) were observed in UIP-CTD patients. In immunohistochemistry analysis, elevated expression of HE4 in bronchiolar epithelium and mesenchyme was observed in patients with UIP-RA compared with controls. The serum levels of HE4 (≥277.5 pmol/L) and GAP index were related to an increased risk of mortality (HR = 3.884, p = 0.034; HR = 1.480, p = 0.028, respectively).
CONCLUSIONS: The expression of HE4 in serum and lung specimens was significantly elevated in UIP-CTD patients. Moreover, serum HE4 may be utilized as a biomarker to evaluate the severity of disease and predict the prognosis of UIP-CTD patients.
摘要：
背景：先前在特发性肺纤维化（IPF）中描述了人附睾蛋白4（HE4）的过表达，但血清HE4是否可被认为是结缔组织疾病相关性间质性肺病(CTD-ILD)伴常见间质性肺炎(UIP)模式的潜在生物标志物,目前尚不清楚.
方法：本研究共纳入55例CTD-ILD患者（UIP-CTD）和52例健康对照。在两个队列中评估了HE4和KrebsvondenLungen-6（KL-6）的血清水平。此外,对6例类风湿性关节炎相关UIP（UIP-RA）患者和6例早期肺癌患者的肺切片进行了HE4的免疫组织化学分析作为正常对照。
结果：UIP-CTD患者的血清HE4和KL-6水平高于健康对照组（HE4为292.3pmol/L对79.5pmol/L，p<0.001；KL-6为1091.0IU/mL对171.5IU/mL，p<0.001）。血清HE4水平与预测的强迫肺活量百分比（FVC％）之间存在显着相关性（r=-0.425，p=0.004），肺一氧化碳的预测扩散能力百分比（DLCO%）（r=-0.447，p=0.003），在UIP-CTD患者中观察到性别-年龄-生理学（GAP）指数（r=0.494，p<0.001）。在免疫组织化学分析中，与对照组相比，UIP-RA患者的细支气管上皮和间充质中HE4的表达升高。血清HE4水平（≥277.5pmol/L）和GAP指数与死亡风险增加相关（HR=3.884，p=0.034；HR=1.480，p=0.028）。
结论：UIP-CTD患者血清和肺标本中HE4的表达明显升高。此外，血清HE4可作为评价UIP-CTD患者疾病严重程度和预测预后的生物标志物。
方法：本研究共纳入55例CTD-ILD患者（UIP-CTD）和52例健康对照。在两个队列中评估了HE4和KrebsvondenLungen-6（KL-6）的血清水平。此外,对6例类风湿性关节炎相关UIP（UIP-RA）患者和6例早期肺癌患者的肺切片进行了HE4的免疫组织化学分析作为正常对照。
结果：UIP-CTD患者的血清HE4和KL-6水平高于健康对照组（HE4为292.3pmol/L对79.5pmol/L，p<0.001；KL-6为1091.0IU/mL对171.5IU/mL，p<0.001）。血清HE4水平与预测的强迫肺活量百分比（FVC％）之间存在显着相关性（r=-0.425，p=0.004），肺一氧化碳的预测扩散能力百分比（DLCO%）（r=-0.447，p=0.003），在UIP-CTD患者中观察到性别-年龄-生理学（GAP）指数（r=0.494，p<0.001）。在免疫组织化学分析中，与对照组相比，UIP-RA患者的细支气管上皮和间充质中HE4的表达升高。血清HE4水平（≥277.5pmol/L）和GAP指数与死亡风险增加相关（HR=3.884，p=0.034；HR=1.480，p=0.028）。
结论：UIP-CTD患者血清和肺标本中HE4的表达明显升高。此外，血清HE4可作为评价UIP-CTD患者疾病严重程度和预测预后的生物标志物。
