Institute of Pathology, Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
Department of Urology, Semmelweis University, 1082 Budapest, Hungary.
Curr Mol Med. 2022;22(10):941-949. doi: 10.2174/1566524021666210225100041.
Expression levels of collagens have been implicated in the progression of various cancers and interaction with cytokeratins but are not well studied in bladder cancer (BC). Therefore, we analyzed the gene and protein expression levels of collagen 1A1 (Col1a1/COL1A1), collagen 3A1 (col3a1/COL3A1), collagen 5A2 (col5a2/COL5A2), cytokeratin 14 (krt14/CK14), and cytokeratin 17 (krt17/CK17) in urothelial BC samples of different stages.
In total, 102 fresh frozen and 190 formalin-fixed and paraffin-embedded (FFPE) samples were tested using immunohistochemistry and RT-qPCR. Expression levels were correlated with clinicopathological and follow-up data.
Col1a1, col3a1, col5a2 and krt14 mRNA levels were significantly overexpressed in high-grade and muscle-invasive BC (MIBC) compared to low-grade and non-muscle invasive BC (NMIBC) cases. Disease-specific survival (DSS) was shorter in patients with high expression levels of col1a1 (p = 0.004), col3a1 (p = 0.004), and col5a2 (p = 0.028). CK14 (p = 0.020), COL3A1 (p = 0.006), and Col5A2 (p = 0.006) protein expression levels were significantly higher and protein expression levels of CK17 (p = 0.05) were significantly lower in MIBC compared to NMIBC. Furthermore, CK14 (p = 0.002) and COL5A2 (p = 0.006) protein expression level were significantly higher in high-grade compared to low-grade BC. DSS was shorter in patients with high expression levels of COL5A2 (p = 0.033) and CK14 (p = 0.042).
Expression changes of collagens and cytokeratins are univariable prognostic markers in BC.
胶原蛋白的表达水平与各种癌症的进展有关，与细胞角蛋白相互作用，但在膀胱癌（BC）中研究甚少。因此，我们分析了不同分期的尿路上皮 BC 样本中胶原蛋白 1A1（Col1a1/COL1A1）、胶原蛋白 3A1（col3a1/COL3A1）、胶原蛋白 5A2（col5a2/COL5A2）、细胞角蛋白 14（krt14/CK14）和细胞角蛋白 17（krt17/CK17）的基因和蛋白表达水平。
共检测了 102 例新鲜冷冻和 190 例福尔马林固定石蜡包埋（FFPE）样本，采用免疫组化和 RT-qPCR 进行检测。表达水平与临床病理和随访数据相关。
与低级别和非肌层浸润性 BC（NMIBC）相比，高级别和肌层浸润性 BC（MIBC）中 Col1a1、col3a1、col5a2 和 krt14 mRNA 水平明显过表达。Col1a1（p = 0.004）、col3a1（p = 0.004）和 col5a2（p = 0.028）高表达患者的疾病特异性生存率（DSS）更短。与 NMIBC 相比，MIBC 中 CK14（p = 0.020）、COL3A1（p = 0.006）和 Col5A2（p = 0.006）蛋白表达水平显著升高，CK17 蛋白表达水平（p = 0.05）显著降低。此外，高级别 BC 中 CK14（p = 0.002）和 COL5A2（p = 0.006）蛋白表达水平明显高于低级别 BC。COL5A2（p = 0.033）和 CK14（p = 0.042）高表达患者的 DSS 更短。
胶原蛋白和细胞角蛋白的表达变化是 BC 的单变量预后标志物。
