Proteomic profiling identifies novel diagnostic biomarkers and molecular subtypes for mucinous tubular and spindle cell carcinoma of the kidney.
Proteomic profiling identifies novel diagnostic biomarkers and molecular subtypes for mucinous tubular and spindle cell carcinoma of the kidney.
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DOI：
10.1002/path.5869
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发表时间：
2022-05
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影响因子：
--
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中科院分区：
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粘液管状和梭形细胞癌（MTSCC）是一种相对罕见的肾上皮肿瘤，在形态和免疫组织化学上类似于1型乳头状肾细胞癌（PRCC）。MTSCC的准确诊断仍然是一个挑战。在这里，通过蛋白质组学分析，我们对MTSCC和PRCC进行了表征，以确定诊断性生物标志物。我们发现，与MTSCC邻近正常组织或PRCC肿瘤的蛋白质组相比，MTSCC肿瘤蛋白质组在B细胞介导的免疫中显著富集。重要的是，我们鉴定出MZB1、VCAN和SOSTDC1作为诊断性生物标志物，将MTSCC与1型PRCC的实体变体区分开来，合并后的AUC为0.985。MZB1与肿瘤临床分期呈负相关，可能通过激活补体系统发挥抗肿瘤作用。最后，无监督聚类揭示了MTSCC的两种分子亚型，表现出不同的形态、氧化磷酸化的表达特征和加重。总之，我们的分析确定了MTSCC的三蛋白诊断组和分子亚型。©2022作者。《病理学杂志》由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版。
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that the MTSCC tumor proteome was significantly enriched in B‐cell‐mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from the solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti‐tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three‐protein diagnostic panel and molecular subtypes for MTSCC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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影响因子：
23.4
作者：
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通讯作者：
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DOI：
10.1164/rccm.201309-1611oc
发表时间：
2014-04-01
影响因子：
24.7
作者：
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通讯作者：
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