Gabriela Gremel, Dijana Djureinovic, Marjut Niinivirta, Alexander Laird, Oscar Ljungqvist, Henrik Johannesson, Julia Bergman, Per-Henrik Edqvist, Sanjay Navani, Naila Khan, Tushar Patil, Åsa Sivertsson, Mathias Uhlén, David J. Harrison, Gustav J. Ullenhag, Grant D. Stewart, Fredrik Pontén
Abstract
There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC).
Human Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival.
CUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203-0.719, P = 0.003).
CUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 September 2021.
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Altmetric has tracked 22,925,760 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 8,333 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done well, scoring higher than 75% of its peers.
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