Background and Objectives: The worldwide incidence of renal cell carcinoma (RCC) rose by 22% between 2012 and 2022. In Australia, RCC accounted for 2.8% of all cancer diagnoses and contributing to 1.8% of cancer-related deaths. Identification of RCC biomarkers may aid in diagnosis and management.Methods: A systematic review of immunohistochemical markers of RCC studies published between 1990 and 2019 was undertaken to select candidate biomarkers of RCC. Immunohistochemical staining of 73 clear cell RCC tumors and paired normal tissue was undertaken using selected markers. Semi-quantitative and quantitative analysis of staining intensity between paired samples was undertaken to evaluate utility as potential biomarkers, using Chi-square tests and pairedt-tests for analysis. As an exploratory analysis, staining intensity was also compared on clinical/demographic variables using linear and logistic regression.Results: There were 123 candidate biomarkers identified in 91 studies. Four candidate markers were selected for further investigation: aminopeptidase A (APA)/cluster of differentiation (CD)249, aminopeptidase N (APN)/CD13, gamma-glutamyl transferase (GGT), and neuron-specific enolase (NSE). APA, GGT, and APN all demonstrated reduced staining intensity in the tumor compared with normal tissue (p< 0.001 for all). NSE demonstrated a statistically significant increase in expression in tumor compared with normal tissue (p< 0.001), and this was more pronounced in patients aged >60 years (p= 0.038).Conclusions: The utility of APA, APN, and GGT as diagnostic biomarkers in clear cell RCC is limited. NSE may have some role as a biomarker for clear cell RCC, particularly among older patients; however, further investigation is required.
背景与目的：2012年至2022年间，全球肾细胞癌发病率上升了22%。在澳大利亚，肾细胞癌占所有癌症诊断的2.8%，并导致1.8%的癌症相关死亡。肾细胞癌生物标志物的识别可能有助于诊断和治疗。方法：对1990年至2019年间发表的肾细胞癌免疫组织化学标志物研究进行系统综述，以筛选候选生物标志物。使用选定的标志物对73例透明细胞肾细胞癌肿瘤及配对正常组织进行免疫组织化学染色。采用卡方检验和配对t检验，对配对样本间的染色强度进行半定量和定量分析，以评估其作为潜在生物标志物的效用。作为探索性分析，还使用线性和逻辑回归比较了染色强度与临床/人口统计学变量之间的关系。结果：在91项研究中确定了123个候选生物标志物。筛选出4个候选标志物进行进一步研究：氨肽酶A（APA）/分化簇（CD）249、氨肽酶N（APN）/CD13、γ-谷氨酰转移酶（GGT）和神经元特异性烯醇化酶（NSE）。与正常组织相比，APA、GGT和APN在肿瘤中的染色强度均降低（p值均<0.001）。NSE在肿瘤中的表达较正常组织显著增加（p<0.001），且在年龄>60岁的患者中更为明显（p=0.038）。结论：APA、APN和GGT作为透明细胞肾细胞癌诊断生物标志物的效用有限。NSE可能作为透明细胞肾细胞癌的生物标志物具有一定作用，尤其在老年患者中；然而，仍需进一步研究。
Biomarkers in Renal Cell Carcinoma: A Systematic Review and Immunohistochemical Validation Study
肿瘤(癌症)患者之家