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.

Osteosarcoma (OS) is a primary malignant bone tumor most commonly affecting children and adolescents and is characterized by loss of differentiation. Bone morphogenetic protein/retinoic acid inducible neural-specific 3 (BRINP3) has been reported to regulate the differentiation of osteoblasts. However, the role that BRINP3 plays in the progression of osteosarcoma remains unknown. We found in this study that BRINP3 was highly expressed in 64.13% of human osteosarcoma tissues and it was associated with histological grade, tumor recurrence, and poor clinical prognosis of osteosarcoma. In vitro, downregulation of BRINP3 was able to inhibit the proliferation and invasion of osteosarcoma cell lines. Furthermore, BRINP3 interacted with microtubule-associated protein 4 (MAP4) at the protein level, and overexpression of MAP4 could partially reverse the inhibitory effect of downregulated BRINP3 on the proliferation and invasion of osteosarcoma cells, which indicates that downregulation of BRINP3 might suppress the proliferation and invasion of osteosarcoma cells by inhibiting MAP4 expression. Overall, our results demonstrate that BRINP3 functions as an oncogene within osteosarcoma through MAP4 and could therefore be used as a potential biomarker for osteosarcoma diagnostics and therapeutics.

Purpose Although papillary renal cell carcinoma (PRCC) has a relatively favorable prognosis, a small number of patients with lymph node or distant metastasis have a poor prognosis. Owing to the complex typing and heterogeneity of PRCC, it remains difficult to provide risk stratification. The objective of our research was to identify potential markers of PRCC prognosis. Methods We performed proteomics and bioinformatics analyses on six pairs of formalin‐fixed paraffin‐embedded tumor and paired normal tissue samples. The Cancer Genome Atlas (TCGA) data were used to analyze the prognostic value of differentially expressed proteins (DEPs) in PRCC. We verified the expression of the major biomarker through immunohistochemistry (IHC) in 91 PRCC tumor specimens. Results Proteomic analysis revealed 1544 DEPs between tumor and paired normal tissues. PRCC transcriptomic data from the TCGA database revealed that compared to non‐tumor tissues, the expression of high‐mobility group protein A2 (HMGA2) was upregulated in tumor tissues, and patients with high HMGA2 expression exhibited shorter overall survival times. HMGA2 was associated with PRCC tissue subtype and higher cell pleomorphism. Both TCGA and IHC results showed that HMGA2 expression was associated with lymph node metastasis and clinical stage. Conclusion HMGA2 was positively correlated with malignant progression and could be a valuable novel prognostic biomarker for PRCC risk stratification.