Prognostic biomarkers in renal cell carcinoma

A hallmark of renal cell carcinoma is its variable prognosis. Surgical resection of primary renal cell carcinoma can be curative when the disease is localized. However, approximately 20% of patients with early stages of localized renal cell carcinomas subsequently develop metastasis after the primary tumor is removed. The median survival for patients with metastatic disease is approximately 13 months. Therefore, there is a great need for biomarkers to predict metastasis and prognosis. Many prognostic biomarkers were studied in the past decade. In recent years, several promising biomarkers, including CAIX, B7-H1 and IMP3, have also been identified by large retrospective studies. Further validation of these biomarkers is essential to transfer the research data into clinical practice. Eventually, an outcome prediction model with biomarkers, staging system and other risk factors will identify high-risk patients with likelihood of progression and formulate different follow-up protocols or systematic treatments for these patients.     

Identification of potential biomarkers associated with immune infiltration in papillary renal cell carcinoma

BackgroundImmunotherapeutic approaches have recently emerged as effective treatment regimens against various types of cancer. However, the immune‐mediated mechanisms surrounding papillary renal cell carcinoma (pRCC) remain unclear. This study aimed to investigate the tumor microenvironment (TME) and identify the potential immune‐related biomarkers for pRCC.MethodsThe CIBERSORT algorithm was used to calculate the abundance ratio of immune cells in each pRCC samples. Univariate Cox analysis was used to select the prognostic‐related tumor‐infiltrating immune cells (TIICs). Multivariate Cox regression analysis was performed to develop a signature based on the selected prognostic‐related TIICs. Then, these pRCC samples were divided into low‐ and high‐risk groups according to the obtained signature. Analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the biological function of the DEGs (differentially expressed genes) between the high‐ and low‐risk groups. The hub genes were identified using a weighted gene co‐expression network analysis (WGCNA) and a protein‐protein interaction (PPI) analysis. The hub genes were subsequently validated by multiple clinical traits and databases.ResultsAccording to our analyses, nine immune cells play a vital role in the TME of pRCC. Our analyses also obtained nine potential immune‐related biomarkers for pRCC, including TOP2A, BUB1B, BUB1, TPX2, PBK, CEP55, ASPM, RRM2, and CENPF.ConclusionIn this study, our data revealed the crucial TIICs and potential immune‐related biomarkers for pRCC and provided compelling insights into the pathogenesis and potential therapeutic targets for pRCC.     

高原地区单中心五年肾癌临床病理特点分析

目的分析高原地区单中心近5年收治的肾细胞癌患者的临床病理特点。 方法收集2017年1月1日至2021年12月31日期间于西藏自治区人民医院泌尿外科住院行手术治疗且术后标本病理学被明确诊断为肾细胞癌患者的临床病理资料,分析肾细胞癌患者的一般资料、肿瘤大小、病理学特点、TNM分期、临床表现及分期、手术情况。 结果68例肾细胞癌患者中男性43例（63.2%）,女性25例（36.8%）,男女比例为1.72∶1。发病年龄范围为22~85岁,中位年龄为56.5（50.0~61.8）岁,高发年龄段为50~70岁（72.1%）。68例肾细胞癌患者中藏族患者66例（97.0%）,门巴族患者1例（1.5%）,回族患者1例（1.5%）;城镇地区患者20例（29.4%）,农村地区患者48例（70.6%）,城乡比例约为1∶2.4。68例肾细胞癌患者中通过体检或检查发现29例（42.6%）,出现相关临床症状后就诊者39例（57.4%）。主要病理类型为肾透明细胞癌55例（80.9%）。68例肾细胞癌患者中行腹腔镜辅助下根治性肾切除术45例（66.2%）,腹腔镜辅助下肾部分切除术14例（20.6%）,开放根治性肾切除术5例（7.4%）,开放肾部分切除术2例（2.9%）,腹腔镜中转开放根治性肾切除术2例（2.9%）,其中腹腔镜经腰入路44例（64.7%）,腹腔镜经腹入路15例（22.1%）。 结论本中心主要为藏族患者,主要病理类型仍为肾透明细胞癌。男性患者比例高于女性,农村地区病例数为城市地区的2.4倍,高发年龄段为50~70岁。有临床症状就诊者占比较高,主要术式为经腰入路腹腔镜辅助下根治性肾切除术。     

Role of metabolomics-derived biomarkers to identify renal cell carcinoma: a comprehensive perspective of the past ten years and advancements

ABSTRACT

Introduction: Renal cell carcinoma (RCC) is one of the most prevalent metabolic diseases and a leading cause of utmost mortality among men globally. In spite of extensive development in technology for biomarker discovery during the last 10 years, the currently used clinical biomarkers are still unable to detect RCC at early and progression stages. Hence, the development of new and precise biomarkers is most important to improve the clinical management of RCC and reduce the level of mortality.

Area covered: For the detection of RCC at an early stage; a new branch of omics technology – metabolomics – has been introduced. Mainly two techniques (mass spectrometry and nuclear magnetic resonance spectroscopy) have been exploited to execute metabolomics. Precisely, metabolomics showed promising and powerful approach to identify novel RCC biomarker. The present review discussed and the literature search to narrate the outcomes of the past 10 years of studies related to RCC pathophysiology, metabolomics, advancements, and shortcomings.

Expert opinion: Although, compared to mass spectrometric tactic, nuclear magnetic resonance is moving fast to achieve the aim and in vivo application for diagnosis and management of RCC, metabolomics-based research in RCC is still in its infancy stage.     

7例转移性透明细胞性肾细胞癌的诊断及鉴别诊断

目的 描述肺、肾上腺、甲状腺转移性透明细胞性肾细胞癌（RCCs）的病理特点，探讨其诊断及鉴别诊断。方法 应用HE和免疫组化方法，对7例转移性透明细胞性RCCs及其中5例的肾原发性癌染色并观察。结果 转移性透明细胞性RCCs组织学具有实性巢状、有／无腔的腺泡状及腺管状结构，间质少且富于血管。免疫组化示全部转移性及原发性透明细胞性RCCs表达CD10、CK和vimentin。结论 在肿瘤发生部位特异性抗体阴性表达的情况下，结合肿瘤组织学特征，应考虑转移性透明细胞性RCCs。CD10是鉴别转移性透明细胞性RCCs的首选抗体。     

CEUS鉴别诊断肾透明细胞癌和嫌色细胞癌

目的 探讨CEUS对肾透明细胞癌（CCRCC）和嫌色细胞癌（ChRCC）的鉴别诊断价值。方法 收集接受肾脏CEUS检查并经术后病理证实为CCRCC的患者75例及ChRCC的患者26例。观察CCRCC和ChRCC的增强方式、增强程度、增强形态、假包膜征及病灶对局部淋巴结、肾包膜及肾静脉的侵犯情况,并绘制时间-强度曲线,获得校正的始增时间（ΔAT）、达峰时间（ΔTTP）和峰值强度（ΔPI）,进行统计学分析。结果 CCRCC多表现高增强（41/75,54.67%）、弥漫性增强（54/75,72.00%）和不均匀增强（58/75,77.33%）,56.00%（42/75）有假包膜征。ChRCC多表现为低增强（19/26,73.08%）、向心性增强（14/26,53.85%）和均匀增强（17/26,65.38%）,61.54%（16/26）有假包膜征。CCRCC与ChRCC增强程度、增强方式及增强形态的差异均有统计学意义（P均<0.05）,假包膜征检出率的差异无统计学意义（P>0.05）。CCRCC的ΔAT和ΔTTP与ChRCC比较,差异均无统计学意义（P均>0.05）,而CCRCC的ΔPI明显高于ChRCC（P<0.001）。以ΔPI=0.05%为阈值鉴别诊断CCRCC和ChRCC的准确率最高,其敏感度为82.70%,特异度为100%,ROC曲线下面积为0.969。CCRCC出现肾周和（或）肾窦脂肪受累和肾门和（或）腹膜后淋巴结转移的百分率均高于ChRCC（P均<0.05）。结论 CCRCC和ChRCC具有不同的CEUS特征,有助于二者的鉴别诊断。     

miR-34a通过调控YY1抑制肾癌细胞的增殖及侵袭

目的探讨miR-34a在肾癌组织中表达、miR-34a对人肾癌ACHN细胞增殖和侵袭的影响及调控机制。方法实时聚合酶链反应(PCR)检测miR-34a在20例肾癌及癌旁组织中的表达;采用脂质体转染法将miR-34a mimics转染入肾癌ACHN细胞中,试验分空白对照组、阴性对照组、miR-34a mimics转染组。实时PCR检测转染24 h后miR-34a表达量;噻唑蓝(MTT)试验检测细胞增殖;流式细胞术检测细胞周期;Transwell及Matrigel检测细胞侵袭能力;实时PCR和蛋白质印迹(Western blot)技术检测转染后转录因子YY1表达水平。结果与癌旁组织相比,20例癌组织中miR-34a平均表达量为1.06±0.67,显著低于癌旁组织(1.62±0.83,P<0.01);转染后24 h,miR-34a mimics转染组的miR-34a表达量为157.04±13.01,较阴性对照组显著上调(P<0.01);miR-34a mimics转染组细胞增殖能力显著降低(P<0.01),细胞生长被阻滞在G0/G1期;细胞侵袭能力明显减弱(P<0.01);转染miR-34a mimics后YY1基因在mRNA表达无明显变化(P>0.05),蛋白水平下调。结论 miR-34a在肾癌中低表达,可能与肾癌的发生有关;miR-34a调控YY1的表达可能是抑制肾癌细胞生物活性的重要机制之一。     

Baseline perfusion CT parameters as potential biomarkers in predicting long-term prognosis of localized clear cell renal cell carcinoma

Purpose

We aimed to explore the relationship among baseline perfusion CT parameters, clinical, and pathological factors with post-nephrectomy long-term progression-free survival in localized clear cell renal cell carcinoma.

Materials and methods

This study retrospectively collected 127 patients from March 2005 to May 2007 who undertook perfusion CT. 61 patients were confirmed of pT1N0M0 or pT2N0M0 ccRCC. The mean follow-up time is 118.8 months (± 13.1 m, range 72–135 m). We compared clinical, pathological factors (gender, T stage, age, Fuhrmann grade, VEGF level, and MVD), and perfusion parameters before treatment [blood flow (BF), blood volume, mean transition time, and permeability surface-area product] between groups with post-nephrectomy metastasis and without metastasis. Association between covariates and progression-free survival (PFS) were analyzed using Cox proportional regression.

Results

Among 61 patients, 11 developed distant metastasis (10 in the lung, one in the bone). BF in metastatic group [429.1 (233.8, 570.1) ml/min/100 g] was significantly higher than non-metastatic group [214.3 (153.3, 376.5) ml/min/100 g] (p = 0.011). Metastatic group also had more patients with higher Fuhrmann grade. Multi-covariant Cox regression demonstrated T staging, Fuhrmann grade, and BF were significantly associated with PFS [hazard ratio (HR) 3.35, 3.08, and 1.006]. In another model, BF > 230 ml/min/100 g was associated with PFS (HR 12.90), along with T staging and Fuhrmann grade (HR 4.73, 3.69).

Conclusion

Baseline tumor BF is a potential biomarker in prediction long-term metastasis of localized ccRCC and may help screening for higher risk localized ccRCC patients who need personalized surveillance strategy after nephrectomy.

     

多房性囊性肾细胞癌临床病理分析

目的探讨多房性囊性肾细胞癌（MCRCC）的临床病理特点及手术方式与预后的关系。方法对2例MCRCC进行病理形态及免疫组化观察,结合文献分析其临床特点及手术方式与预后的关系。结果2例MCRCC肿瘤直径均〈4cm。镜下见肿瘤全部由大小不等的囊腔构成,囊腔内衬透明细胞,间隔内透明细胞呈巢状分布,Fuhrman分级为Ⅰ～Ⅱ级,囊腔间隔内可见似平滑肌的梭形细胞。免疫组化标记：透明细胞CK（广谱）（＋）,CD68和Ki-67（-）;间隔内梭形细胞SMA（＋）。1例行根治性肾切除术,1例行肿瘤剜除术,随访2～26个月,均无复发及转移。结论MCRCC是具有低度恶性潜能的肿瘤,有其独特的病理形态特征,肿瘤预后良好,可通过手术切除而治愈。〈4cm的肿瘤,可以施行保守性手术治疗。     

多房性囊性肾细胞癌临床病理分析

目的 探讨多房性囊性肾细胞癌（MCRCC）临床病理特点及鉴别诊断要点,并对国内外相关文献进行复习,以提高对MCRCC的认识和病理诊断水平.方法 分析1例MCRCC患者的临床表现、组织形态学特征及免疫组化表型,并检索国内外相关文献报道共522例,总结MCRCC的特点.结果 患者男,50岁,因体检时发现左肾占位入院,MRI、彩超及CT检查考虑为错构瘤.病理检查：大体示肿瘤位于左肾上极,有完整包膜,大小4.5 cm×4.2 cm ×4.0 cm,剖面见肿瘤由大小不等的多个囊腔构成,囊腔间隔厚薄不均,囊壁尚光滑.镜检示囊腔内衬单层透明细胞,囊腔间隔胶原纤维增生,可见灶性钙化,间隔内可见巢片状分布的透明细胞,但未形成肉眼可见的结节.细胞异型性小,细胞核Fuhrman分级：Ⅰ级.免疫组化标记显示囊腔上皮及间隔内肿瘤细胞CK和EMA阳性,CD10、RCC、Ki67和CD68阴性.行后腹腔镜下左肾根治性切除术,随访8个月,一般情况好,未见复发和转移.结论 MCRCC作为肾细胞癌的一种少见的独立亚型,完全由囊腔构成,影像学和穿刺细胞学检查等难以与囊性相关性肾病区别,因此准确的病理诊断非常必要,免疫组化标记对其诊断及鉴别诊断具有肯定价值.该肿瘤具有低度恶性潜能,预后良好,保留肾单位手术值得考虑.     

Beyond renal cell carcinoma: rare and unusual renal masses

The vast majority of primary renal masses represent clear cell or papillary renal cell carcinomas, angiomyolipomas, or transitional cell carcinomas. However, a number of more rare masses can also be encountered, many of which can be very difficult to differentiate from these more common entities based on their imaging features. These uncommon entities include metanephric adenoma, epithelioid angiomyolipoma, medullary renal cell carcinomas, multilocular cystic nephroma, hemangiopericytoma, hemangioma, leiomyoma, leiomyosarcoma, solitary fibrous tumor, renal plasmacytomas, and mixed epithelial and stromal tumors. In some cases, certain clinical and imaging features can allow one of these unusual entities to be placed in the differential diagnosis, including patient age, degree of tumor enhancement, presence of underlying sickle cell trait or sickle cell disease, the presence of a cystic component to the tumor, and tumor morphology. Even if a radiologist is unable to make a specific diagnosis, knowledge of these entities is important, as it allows radiologists to guide post-surgical follow-up, as well to understand the most common sites of metastatic disease.     

Identification of prognostic biomarkers in papillary renal cell carcinoma and PTTG1 may serve as a biomarker for predicting immunotherapy response

ObjectiveThis study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC).MethodsTwo microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort.ResultsEight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with patients’ prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p < .001; HR = 2.673, p = .001). And higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in the FUSCC cohort (χ²=3.99, p < .05).ConclusionsEight genes were identified as a prognostic biomarker and the expression level of PTTG1 was also found to serve as a potential predictor for ICB response in pRCC patients.

Key messages:

• Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with pRCC patients’ prognosis.
• Expression level of PTTG1 was significantly associated with tumour microenvironment including lymphocytes, immunomodulators, and chemokines.
• Higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in FUSCC cohort

     

Comprehensive overview of axitinib development in solid malignancies: focus on metastatic renal cell carcinoma

The landscape of treatment for metastatic renal cell carcinoma (mRCC) continues to evolve. Although several new drugs have been approved for the treatment of this disease in recent years, mRCC remains incurable. Thus, the search continues for new effective therapies. One such novel compound is axitinib (Inlyta, Pfizer), a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor. Following phase I testing in advanced solid tumors (where hypertension, stomatitis, and diarrhea were the dose-limiting toxicities), use of axitinib has been further developed through phase II testing in thyroid, breast, lung, and renal cancers. Recently, the phase III AXIS (Axitinib [AG 013736] as Second Line Therapy for Metastatic Renal Cell Cancer) trial demonstrated an improvement in progression-free survival for patients with mRCC who were treated with axitinib versus sorafenib (Nexavar, Bayer) as second-line therapy. This article describes the preclinical and clinical evolution of axitinib, with an emphasis on its development and role in mRCC.     

RFA of renal cell carcinoma in a solitary kidney

The incidence of renal cell carcinoma (RCC) is increasing worldwide and diagnosis is made in an earlier stage due to increasing use of CT and ultrasound. Patients with a history of RCC have a high risk to develop another RCC within their remaining kidney. Especially, patients after tumor nephrectomy have to undergo follow-up examinations regularly allowing an early detection of new RCCs. Especially in patients with solitary kidney gold standard therapy (nephron-sparing surgery) can often account for consecutive renal failure with the need for hemodialysis. Percutaneous radiofrequency ablation (RFA) gained worldwide acceptance for the treatment of liver tumors in patients unable to undergo surgery. Furthermore, during the past few years, there is an increasing amount of publications dealing with the effectiveness of minimally invasive therapies like RFA in patients with renal masses. However, in the subgroup of patients with solitary kidney suffering from RCC, there are only case reports regarding safety and midterm outcome available so far. Therefore, the aim of this article is to briefly describe the basic technical principles of RFA and then focus on indications, technique, safety and the midterm outcome after treatment in terms of renal function and relapse.     

Cardiac metastasis from a renal cell carcinoma

Renal cell carcinomas are known to extend into the renal vein and inferior vena cava, but cardiac metastases are rare and usually clinically silent. In the case described here, there was evidence of right ventricular outflow obstruction, associated with a metastatic renal tumour in the right ventricular wall protruding into the ventricular cavity. The patient had presented years earlier with an ulnar neuropathy, for which the tumour may have been responsible. This case highlights the need to consider an underlying paraneoplastic syndrome in a patient presenting with neuropathy, because appropriate investigation could have led to early detection and possible cure of the renal lesion. When renal cell carcinoma is confined to the renal parenchyma, five-year survival is up to 70%, but this falls to 5% in the presence of distant metastases.     

肾集合管癌合并肾囊性透明细胞癌1例报告及文献复习

目的：探讨肾集合管癌（CDC）合并肾囊性透明细胞癌的临床病理特征及其诊断、鉴别诊断方法。方法：分析1例CDC合并肾囊性透明细胞癌患者的临床表现、组织形态学和免疫表型特征,并复习相关文献。结果：患者,男性,70岁,临床表现为无痛性血尿。影像学检查提示左肾占位。组织学示肾上极的肿瘤组织排列成不规则腺管状、乳头状,部分肿瘤细胞呈靴钉状突向腺腔内,间质纤维结缔组织明显增生,大量淋巴细胞浸润,肿瘤周围部分集合管腺上皮见异型增生。瘤细胞阳性表达波形蛋白（vimentin）、角蛋白7（CK7）、角蛋白19（CK19）、上皮膜抗原（EMA）、转录因子E3（TFE3）和E-钙黏素（E-cad）,而角蛋白20（CK20）、CD31、CD34、CD10、CD117、肾脏特异性钙黏蛋白（ksp-cad）和α-甲基酰基辅酶A消旋酶（AMACR）表达则呈阴性。肾中部囊性肿瘤组织学表现为典型的肾囊性透明细胞癌,癌细胞阳性表达CD10、波形蛋白和CK19,而CK7、CD117表达则呈阴性。结论：CDC是一种少见的高度恶性肿瘤,其诊断依赖组织病理学和免疫组化标记。由于组织起源不同,CDC合并肾透明细胞癌的概率更小,但这种合并存在的情况仍有可能。     

Radiogenomics in renal cell carcinoma

Abdominal Radiology - Radiogenomics, a field of radiology investigating the association between the imaging features of a disease and its gene expression pattern, has expanded considerably in the...