{"title":"肾细胞癌患者 Klotho 表达的预后意义。","authors":"Kumar Rajiv Ranjan, Shrawan Kumar Singh, Nandita Kakkar, Ravimohan Mavuduru","doi":"10.1177/03915603241248303","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Various molecular markers have been investigated in renal cell carcinoma (RCC) without significant reliability. We analyzed Klotho (tumor suppressive protein) expression in RCC to investigate its association with tumor-stage, grade, disease-free-survival (DFS) and overall-survival (OS).</p><p><strong>Methods: </strong>Data of histologically confirmed patients of RCC with complete clinical follow-up were retrieved from Medical-Record-Library. Tissue sections of tumor and normal parenchyma were prepared from the blocks. Immunohistochemical studies for Klotho were done with commercially available kit (EPR6856, Ab181373; Abcam, Cambridge MA, USA). Klotho expression was scored between 0-3 and grouped into weak/absent (0, 1) and moderate/strong (2, 3). Tumors stages and grades were grouped into low stage (I and II) and high stage (III and IV) and into low grade (grade 1 and 2) and high grade (grade 3 and 4) according to WHO/ISUP grading. The histopathologists were blinded as to the clinical and follow-up data. Various prognostic factors were analyzed with respect to Klotho expression. Kaplan-Meier curves were created for DFS and OS.</p><p><strong>Results: </strong>Fifty-four patients of mean age 55.15 ± 13.34 years and M:F ratio of 1.8:1 were included. Normal renal tissue had strong expression of Klotho in all. In tumor tissue 20 (37%) had negative, 7 (13%) had weak, 14 (25.9%) had moderate and 13 (24.1%) had strong Klotho expression. Significantly more patients had absent/weak Klotho expression with higher grade (16/24 (66.7%) vs 7/25 (28%); <i>p</i> = 0.007), higher stage (22/33 (66%) vs 5/21 (23.8%); <i>p</i> = 0.002), LVI (12/14 (85.7%) vs 2/14 (14.3%); <i>p</i> = 0.002), sinus-fat-invasion (16/21 (76.2%) vs 5/21 (23.8%); <i>p</i> = 0.002), renal-vein-involvement (14/18 (77.8%) vs 4/18 (22.2%); <i>p</i> = 0.004), necrosis (17/26 (65.3%) vs 9/26 (34.6%); <i>p</i> = 0.029) and metastasis (8/9 (88.9%) vs 1/9 (11.1%); <i>p</i> = 0.01). Median DFS and OS were significantly lower in patients with weak/absent Klotho expression (12 vs 23 months, <i>p</i> = 0.023 and 15 vs 33 months, <i>p</i> = 0.006 respectively). Kaplan-Meier curves showed lower estimated DFS and OS in patients with weak/absent expression.</p><p><strong>Conclusions: </strong>We conclude that Klotho expression in renal tumor could be a good prognostic marker in patients with RCC.</p>","PeriodicalId":23574,"journal":{"name":"Urologia Journal","volume":" ","pages":"494-499"},"PeriodicalIF":0.8000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prognostic significance of Klotho expression in patients with renal cell carcinoma.\",\"authors\":\"Kumar Rajiv Ranjan, Shrawan Kumar Singh, Nandita Kakkar, Ravimohan Mavuduru\",\"doi\":\"10.1177/03915603241248303\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Various molecular markers have been investigated in renal cell carcinoma (RCC) without significant reliability. We analyzed Klotho (tumor suppressive protein) expression in RCC to investigate its association with tumor-stage, grade, disease-free-survival (DFS) and overall-survival (OS).</p><p><strong>Methods: </strong>Data of histologically confirmed patients of RCC with complete clinical follow-up were retrieved from Medical-Record-Library. Tissue sections of tumor and normal parenchyma were prepared from the blocks. Immunohistochemical studies for Klotho were done with commercially available kit (EPR6856, Ab181373; Abcam, Cambridge MA, USA). Klotho expression was scored between 0-3 and grouped into weak/absent (0, 1) and moderate/strong (2, 3). Tumors stages and grades were grouped into low stage (I and II) and high stage (III and IV) and into low grade (grade 1 and 2) and high grade (grade 3 and 4) according to WHO/ISUP grading. The histopathologists were blinded as to the clinical and follow-up data. Various prognostic factors were analyzed with respect to Klotho expression. Kaplan-Meier curves were created for DFS and OS.</p><p><strong>Results: </strong>Fifty-four patients of mean age 55.15 ± 13.34 years and M:F ratio of 1.8:1 were included. Normal renal tissue had strong expression of Klotho in all. In tumor tissue 20 (37%) had negative, 7 (13%) had weak, 14 (25.9%) had moderate and 13 (24.1%) had strong Klotho expression. Significantly more patients had absent/weak Klotho expression with higher grade (16/24 (66.7%) vs 7/25 (28%); <i>p</i> = 0.007), higher stage (22/33 (66%) vs 5/21 (23.8%); <i>p</i> = 0.002), LVI (12/14 (85.7%) vs 2/14 (14.3%); <i>p</i> = 0.002), sinus-fat-invasion (16/21 (76.2%) vs 5/21 (23.8%); <i>p</i> = 0.002), renal-vein-involvement (14/18 (77.8%) vs 4/18 (22.2%); <i>p</i> = 0.004), necrosis (17/26 (65.3%) vs 9/26 (34.6%); <i>p</i> = 0.029) and metastasis (8/9 (88.9%) vs 1/9 (11.1%); <i>p</i> = 0.01). Median DFS and OS were significantly lower in patients with weak/absent Klotho expression (12 vs 23 months, <i>p</i> = 0.023 and 15 vs 33 months, <i>p</i> = 0.006 respectively). Kaplan-Meier curves showed lower estimated DFS and OS in patients with weak/absent expression.</p><p><strong>Conclusions: </strong>We conclude that Klotho expression in renal tumor could be a good prognostic marker in patients with RCC.</p>\",\"PeriodicalId\":23574,\"journal\":{\"name\":\"Urologia Journal\",\"volume\":\" \",\"pages\":\"494-499\"},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Urologia Journal\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/03915603241248303\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Urologia Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/03915603241248303","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/10 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
导言：对肾细胞癌（RCC）的各种分子标记物进行了研究，但并不十分可靠。我们分析了 Klotho（肿瘤抑制蛋白）在 RCC 中的表达，研究其与肿瘤分期、分级、无病生存期（DFS）和总生存期（OS）的关系：方法：从医学文献数据库（Medical-Record-Library）中检索经组织学确诊并有完整临床随访的 RCC 患者数据。制备肿瘤和正常实质组织切片。使用市售试剂盒（EPR6856, Ab181373; Abcam, Cambridge MA, USA）对 Klotho 进行免疫组化检测。Klotho 表达在 0-3 之间，分为弱/无（0，1）和中/强（2，3）。根据 WHO/ISUP 分级，肿瘤分期和分级分为低分期（I 期和 II 期）和高分期（III 期和 IV 期），以及低分级（1 级和 2 级）和高分级（3 级和 4 级）。组织病理学家对临床和随访数据均为盲人。分析了与Klotho表达有关的各种预后因素。对DFS和OS绘制了Kaplan-Meier曲线：54名患者的平均年龄为（55.15 ± 13.34）岁，男女比例为1.8:1。所有正常肾组织都有 Klotho 的强表达。在肿瘤组织中，20 例（37%）Klotho 表达为阴性，7 例（13%）为弱表达，14 例（25.9%）为中度表达，13 例（24.1%）为强表达。Klotho表达缺失/弱的患者明显多于分级较高（16/24 (66.7%) vs 7/25 (28%)；P = 0.007）、分期较高（22/33 (66%) vs 5/21 (23.8%)；P = 0.002）、LVI（12/14 (85.7%) vs 2/14 (14.3%)；P = 0.002）、窦脂肪浸润（16/21（76.2%） vs 5/21（23.8%）；p = 0.002）、肾静脉浸润（14/18（77.8%） vs 4/18（22.2%）；p = 0.004）、坏死（17/26（65.3%） vs 9/26（34.6%）；p = 0.029）和转移（8/9（88.9%） vs 1/9（11.1%）；p = 0.01）。Klotho弱/无表达患者的中位生存期和手术期明显较低（分别为12个月 vs 23个月，p = 0.023和15个月 vs 33个月，p = 0.006）。Kaplan-Meier曲线显示，弱/无表达患者的估计DFS和OS较低：我们得出结论：肾肿瘤中 Klotho 的表达可作为 RCC 患者的良好预后标志物。
Prognostic significance of Klotho expression in patients with renal cell carcinoma.
Introduction: Various molecular markers have been investigated in renal cell carcinoma (RCC) without significant reliability. We analyzed Klotho (tumor suppressive protein) expression in RCC to investigate its association with tumor-stage, grade, disease-free-survival (DFS) and overall-survival (OS).
Methods: Data of histologically confirmed patients of RCC with complete clinical follow-up were retrieved from Medical-Record-Library. Tissue sections of tumor and normal parenchyma were prepared from the blocks. Immunohistochemical studies for Klotho were done with commercially available kit (EPR6856, Ab181373; Abcam, Cambridge MA, USA). Klotho expression was scored between 0-3 and grouped into weak/absent (0, 1) and moderate/strong (2, 3). Tumors stages and grades were grouped into low stage (I and II) and high stage (III and IV) and into low grade (grade 1 and 2) and high grade (grade 3 and 4) according to WHO/ISUP grading. The histopathologists were blinded as to the clinical and follow-up data. Various prognostic factors were analyzed with respect to Klotho expression. Kaplan-Meier curves were created for DFS and OS.
Results: Fifty-four patients of mean age 55.15 ± 13.34 years and M:F ratio of 1.8:1 were included. Normal renal tissue had strong expression of Klotho in all. In tumor tissue 20 (37%) had negative, 7 (13%) had weak, 14 (25.9%) had moderate and 13 (24.1%) had strong Klotho expression. Significantly more patients had absent/weak Klotho expression with higher grade (16/24 (66.7%) vs 7/25 (28%); p = 0.007), higher stage (22/33 (66%) vs 5/21 (23.8%); p = 0.002), LVI (12/14 (85.7%) vs 2/14 (14.3%); p = 0.002), sinus-fat-invasion (16/21 (76.2%) vs 5/21 (23.8%); p = 0.002), renal-vein-involvement (14/18 (77.8%) vs 4/18 (22.2%); p = 0.004), necrosis (17/26 (65.3%) vs 9/26 (34.6%); p = 0.029) and metastasis (8/9 (88.9%) vs 1/9 (11.1%); p = 0.01). Median DFS and OS were significantly lower in patients with weak/absent Klotho expression (12 vs 23 months, p = 0.023 and 15 vs 33 months, p = 0.006 respectively). Kaplan-Meier curves showed lower estimated DFS and OS in patients with weak/absent expression.
Conclusions: We conclude that Klotho expression in renal tumor could be a good prognostic marker in patients with RCC.
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