Claudin 6 在乳头状肾细胞癌中的预后影响。

The prognostic impact of Claudin 6 in papillary renal cell carcinoma.

机构信息

Department of Rheumatology and Immunology, Hannover Medical School, 30625 Hannover, Germany; Department of Medical Oncology, National Center of Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Institute of Pathology, University Hospital Erlangen-Nuernberg, Friedrich Alexander University (FAU), 91054 Erlangen, Germany; Department of Urology, University Hospital Münster, 48149 Münster, Germany; Department of Urology, University Hospital Göttingen, 37075 Göttingen, Germany; Department of Pathology, University Hospital Göttingen, 37075 Göttingen, Germany; Department of Urology and Pediatric Urology, University Hospital Saarland (UKS), 66421 Homburg, Germany; Department of Urology, University Hospital Marburg, 35037 Marburg, Germany; Department of Urology, University Hospital Heidelberg, 69120 Heidelberg, Germany; Institute of Pathology, University Hospital Mainz, 55131 Mainz, Germany; Department of Urology and Pediatric Urology, University Hospital Erlangen, 91058 Erlangen, Germany; Department of Urology, Marien-Hospital Herne, Ruhr University Bochum, 44625 Herne, Germany; Department of Urology, University Hospital Mainz, 55131 Mainz, Germany; Department of Urology, University Hospital Frankfurt, 60590 Frankfurt/Main, Germany; Department of Urology, University Hospital Regensburg, 93053 Regensburg, Germany; Department for Rheumatology and Immunology, Hannover Medical School, 30625 Hannover, Germany.

Department of Medical Oncology, National Center of Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.

出版信息

Pathol Res Pract. 2022 Mar;231:153802. doi: 10.1016/j.prp.2022.153802. Epub 2022 Feb 11.

DOI:10.1016/j.prp.2022.153802

PMID:35180650

Abstract

BACKGROUND

Claudins are promising biomarkers for diagnosis and prognosis or targets for treatment. They play a major role in signal transduction and are important in nearly all aspects of tumorigenesis. Claudin 6 is a member of the claudin family and is part of the tight junction molecule. It is reactivated in several cancer types and serves as prognostic marker in, for example, gastric, breast or non small cell lung cancer. The prognostic role of Claudin 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), is still unclear.

PATIENTS AND METHODS

The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Claudin 6 was determined by immunohistochemistry.

RESULTS

In total, Claudin 6 staining was positive in 55 of 240 type 1 and 30 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed an overall survival of 84% for Claudin 6- compared to 78% for Claudin 6 + in pRCC type 1 tumors (p = 0.449, log-rank) and 68% for Claudin 6- compared to 65.4% for Claudin 6 + in pRCC type 2 tumors (p = 0.364, log-rank).

CONCLUSION

In this study, claudin 6 expression showed no significant association regarding overall survival (OS) and therefore did not qualify as a prognostic marker in pRCC. Future studies will have to determine, whether Claudin 6 plays a prognostic role in other RCC entities. In addition, the function of Claudin 6 as a predictive marker for therapeutic approaches has to be evaluated in future studies.

摘要

背景

紧密连接蛋白（Claudins）是诊断和预后的有前途的生物标志物，或是治疗的靶点。它们在信号转导中起主要作用，并且在肿瘤发生的几乎所有方面都很重要。Claudin 6 是紧密连接蛋白家族的成员，也是紧密连接分子的一部分。它在几种癌症类型中被重新激活，并作为例如胃癌、乳腺癌或非小细胞肺癌的预后标志物。Claudin 6 在肾细胞癌（RCC）中的预后作用，特别是在乳头状 RCC（pRCC）中，仍然不清楚。

患者和方法

患者样本的采集是 PANZAR 联盟的联合合作。分别从 240 名和 128 名患有 1 型和 2 型 pRCC 的患者中收集了病史和肿瘤标本。通过免疫组织化学法确定 Claudin 6 的表达。

结果

总共，在 240 例 1 型和 128 例 2 型 pRCC 中，Claudin 6 染色分别为 55 例和 30 例阳性。Kaplan-Meier 分析显示，Claudin 6-的总生存率为 84%，而 Claudin 6+的 pRCC 1 型肿瘤为 78%（p=0.449，对数秩），Claudin 6-的总生存率为 68%，而 Claudin 6+的 pRCC 2 型肿瘤为 65.4%（p=0.364，对数秩）。