TMEM27 expression and clinical characteristics and survival in clear cell renal cell carcinoma

Abstract Background Transmembrane protein 27 (TMEM27/collectrin), a glycoprotein and homolog of angiotensin-converting enzyme 2 (ACE2), is a regulator of renal amino acid uptake in the proximal tubule and may have a protective role in hypertension. Two previous reports have shown that the absence of TMEM27 expression in clear cell renal cell carcinoma (ccRCC) correlates with poorer cancer-related survival. We report our findings of TMEM27 expression in ccRCC and clinical outcomes in an independent third cohort. Material and Methods We conducted a retrospective analysis to identify all 321 cases of ccRCC diagnosed between 2010 and 2015 at the University of Rochester Medical Center. The intensity of TMEM27 immunostaining on tumor tissue was semi-quantitatively graded on a scale of 0, 0.5, 1, 1.5, 2, 2.5, and 3 by a single pathologist, and correlated with tumor characteristics and survival. Results There was evidence of metastasis at time of nephrectomy in 36 (11.2%) cases, and at the latest follow-up in 70 (21.8%) cases. As of Spring 2021, 82 (25.5%) had died. TMEM27 staining intensity correlated inversely with various tumor characteristics. Kaplan-Meier survival analysis showed worse overall all-cause mortality (p = 0.02) and disease-free survival (p = 0.028) for tumors without any TMEM27 staining (0) compared to 0.5 or higher by log-rank test. Conclusion The absence of TMEM27 expression is associated with more aggressive tumor characteristics and poorer all-cause mortality and disease-free survival in ccRCC. TMEM27 may be a useful biomarker to assess cancer prognosis. Further studies are needed to better assess if TMEM27 is protective in RCC, and its potential role in active surveillance and prediction of response to target therapy.

摘要 背景 跨膜蛋白27（TMEM27/collectrin）是一种糖蛋白，是血管紧张素转换酶2（ACE2）的同源物，是近端小管中肾脏氨基酸摄取的调节因子，可能在高血压中具有保护作用。先前的两项报告表明，在透明细胞肾细胞癌（ccRCC）中TMEM27表达缺失与较差的癌症相关生存率相关。我们报告在一个独立的第三队列中关于ccRCC中TMEM27表达以及临床结果的研究发现。 材料与方法 我们进行了一项回顾性分析，以确定2010年至2015年在罗切斯特大学医学中心诊断的所有321例ccRCC病例。由一名病理学家对肿瘤组织上的TMEM27免疫染色强度按照0、0.5、1、1.5、2、2.5和3的等级进行半定量评分，并与肿瘤特征和生存率相关联。 结果 在肾切除时，36例（11.2%）病例有转移证据，在最近一次随访时，70例（21.8%）病例有转移证据。截至2021年春季，82例（25.5%）患者死亡。TMEM27染色强度与多种肿瘤特征呈负相关。通过对数秩检验，Kaplan - Meier生存分析显示，与染色强度为0.5或更高相比，无任何TMEM27染色（0）的肿瘤的总体全因死亡率（p = 0.02）和无病生存率（p = 0.028）更差。 结论 在ccRCC中，TMEM27表达缺失与更具侵袭性的肿瘤特征以及较差的全因死亡率和无病生存率相关。TMEM27可能是评估癌症预后的有用生物标志物。需要进一步研究以更好地评估TMEM27在肾细胞癌中是否具有保护作用，以及它在积极监测和预测靶向治疗反应中的潜在作用。