Searching for prognostic biomarkers for small renal masses in the urinary proteome

Abstract

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early‐stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label‐free liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) proteomics approach and targeted parallel‐reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC‐SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)‐SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC‐SRMs (ccRCC‐SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC‐SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC‐SRMs. A two‐protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70–0.93) in distinguishing progressive from nonprogressive ccRCC‐SRMs. Patients (Stage I–IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10−6) compared to patients with no alterations. Our in‐depth proteomic analysis identified novel biomarkers for early‐stage RCC‐SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.

Chaperonin-Containing TCP1 Subunit 6A Is a Prognostic Potential Biomarker That Correlates With the Presence of Immune Infiltrates in Colorectal Cancer

“…COAD is the most common intestinal tumor worldwide, especially in women ( Hassanlou et al, 2019 ), and has been reported to be associated with many oncogenes ( Yin et al, 2017 ). Existing literature reports CCT6A to possess oncogenic features in a various human cancer ( Di Meo et al, 2019 ; Huang et al, 2019 ). This study of bioinformatics analysis of publically available genetic sequencing data was performed to gain further insight into the role of CCT6A in the genetic regulation of COAD.…”

“… Ma et al (2018) showed that CCT6A was involved in the proteogenomic characterization of human colorectal cancer liver metastasis. Di Meo et al (2019) reported that CCT6A was a potential prognostic biomarker in renal cell carcinoma. Klimczak et al (2019) also suggested that CCT6A may be involved in imparting an unfavorable prognosis in breast cancer tumor progression.…”

Transcriptome profiling and proteomic validation reveals targets of the androgen receptor signaling in the BT-474 breast cancer cell line

“…Candidate peptides for 23 proteins were selected using the online comprehensive platforms, Selected Reaction Monitoring Atlas (SRMAtlas) [ 35 ] and neXtProt [ 36 ], which combine peptide information with MS-observed evidence. The peptide selection was based on certain criteria, as previously described [ 37 , 38 ]. In the end, one to two tryptic peptides per protein that showed a satisfactory chromatographic spectrum in Skyline (v.19.1.0.193) were selected for PRM method development (Additional file 1 : Table S5).…”

The Autoantibodies against Tumor-Associated Antigens as Potential Blood-Based Biomarkers in Thyroid Neoplasia: Rationales, Opportunities and Challenges

“…In TBSRTC DC4 nodules, CCT6A-AAbs were capable of detecting borderline and malignant tumors with DSp and DSn values of 100% and 40%, respectively [ 125 ]. Interestingly, more recent studies extensively implicated TCP-1ζ/CCT6A as an oncogenic protein and biomarker of poor prognosis in various human malignancies [ 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ], rendering its cancer-associated immunogenicity highly biologically relevant.…”