循环 LAPTM4B-35 在胰腺导管腺癌中的临床影响。
Clinical impact of circulating LAPTM4B-35 in pancreatic ductal adenocarcinoma.
机构信息
Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149, Münster, Germany.
Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, China.
出版信息
J Cancer Res Clin Oncol. 2019 May;145(5):1165-1178. doi: 10.1007/s00432-019-02863-w. Epub 2019 Feb 18.
PURPOSE
LAPTM4B is upregulated in a wide range of cancers associated with poor prognosis. However, the clinical impact of LAPTM4B as diagnostic and prognostic marker in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Thus, the aim of the present study was to investigate the expression of LAPTM4B as circulating marker in PDAC.
METHODS
Expression analysis of LAPTM4B-35 in pancreatic tissue and preoperative blood serum samples of 169 patients with PDAC UICC Stages I-IV (n = 98), chronic pancreatitis (n = 41), and healthy controls (n = 30) by immunohistochemistry, Western blot, and ELISA. Descriptive and explorative statistical analyses of LAPTM4B-35's potential as diagnostic and prognostic marker in PDAC.
RESULTS
Expression of LAPTM4B-35 was significantly increased in tumor tissue and corresponding blood serum samples of patients with PDAC (each p < 0.001) and it could well discriminate PDAC from healthy controls and chronic pancreatitis (p < 0.001; p = 0.0037). LAPTM4B-35 in combination with CA.19-9 outperforms the diagnostic accuracy with an AUC of 0.903 (p < 0.001), sensitivity of 82%, and specificity of 92%. Kaplan-Meier survival analysis revealed an improved overall survival in PDAC UICC I-IV with low expression of circulating LAPTM4B-35 (17 versus 10 months, p = 0.039) as well as an improved relapse-free survival in curatively treated PDAC UICC I-III (16 versus 10 months; p = 0.037). Multivariate overall and recurrence-free survival analyses identified LAPTM4B-35 as favorable prognostic factor in PDAC patients (HR 2.73, p = 0.021; HR 3.29, p = 0.003).
CONCLUSION
LAPTM4B-35 is significantly deregulated in PDAC with high diagnostic and prognostic impact as circulating tumor marker.
目的
LAPTM4B 在广泛的与预后不良相关的癌症中上调。然而，LAPTM4B 作为胰腺导管腺癌 (PDAC) 的诊断和预后标志物的临床意义尚不清楚。因此，本研究旨在探讨 LAPTM4B 作为 PDAC 循环标志物的表达。
方法
采用免疫组织化学、Western blot 和 ELISA 检测 169 例 PDAC UICC 分期 I-IV 期（n=98）、慢性胰腺炎（n=41）和健康对照（n=30）患者的胰腺组织和术前血清样本中 LAPTM4B-35 的表达情况。对 LAPTM4B-35 在 PDAC 中的诊断和预后标志物的潜在作用进行描述性和探索性统计分析。
结果
LAPTM4B-35 的表达在肿瘤组织和 PDAC 患者的相应血清样本中均显著升高（p<0.001），且能很好地区分 PDAC 与健康对照和慢性胰腺炎（p<0.001；p=0.0037）。LAPTM4B-35 与 CA.19-9 联合使用时，诊断准确性的 AUC 为 0.903（p<0.001），敏感性为 82%，特异性为 92%。Kaplan-Meier 生存分析显示，低循环 LAPTM4B-35 表达的 PDAC UICC I-IV 患者总生存期延长（17 个月与 10 个月，p=0.039），可切除的 PDAC UICC I-III 患者无复发生存期延长（16 个月与 10 个月；p=0.037）。多变量总生存和无复发生存分析显示，LAPTM4B-35 是 PDAC 患者的有利预后因素（HR 2.73，p=0.021；HR 3.29，p=0.003）。
结论
LAPTM4B-35 在 PDAC 中明显失调，作为循环肿瘤标志物具有较高的诊断和预后价值。
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