Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

Abstract

Objective: In order to find low abundant proteins secretome and tumor tissue proteome data have been explored in the last few years for the diagnosis of colorectal cancer (CRC). In this review we aim to summarize the results of studies evaluating markers derived from the secretome and tumor proteome for blood based detection of colorectal cancer. Methods: Observing the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines PubMed and Web of Science databases were searched systematically for relevant studies published up to 18 July 2017. After screening for predefined eligibility criteria a total of 47 studies were identified. Information on diagnostic performance indicators, methodological procedures and validation was extracted. Functions of proteins were identified from the UniProt database and the the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess study quality. Results: Forty seven studies meeting inclusion criteria were identified. Overall, 83 different proteins were identified, with carcinoembryonic Antigen (CEA) being by far the most commonly reported (reported in 24 studies). Evaluation of the markers or marker combinations in blood samples from CRC cases and controls yielded apparently very promising diagnostic performances, with area under the curve >0.9 in several cases, but lack of internal or external validation, overoptimism due to overfitting and spectrum bias due to evaluation in clinical setting rather than screening settings are major concerns. Conclusions: Secretome and tumor proteome-based biomarkers when validated in blood yield promising candidates. However, for discovered protein markers to be clinically applicable as screening tool they have to be specific for early stages and need to be validated externally in larger studies with participants recruited in true screening setting.

Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response

“…The HCSD comprises information on proteomics data published in the field of cancer secretome and tumor microenvironment, and the PPD is one of the largest resources of serum and plasma proteins. The CRC secretome has been investigated in conditional media of CRC cell lines, peritoneal liquid, urine, stool, and serum/plasma from CRC patients 16,24–28 .…”

Spermidine/Spermine N1 -Acetyltransferase-1 as a Diagnostic Biomarker in Human Cancer

“…Because the assay detects a final byproduct (AA), which is not further metabolized, the signal is higher compared with traditional cancer biomarkers. In this regard, the already known blood-based protein biomarkers such as [ 27–34 ] carcinoembryonic antigen, carbohydrate antigen 19-9 l and α-fetoprotein alone are unreliable as well as lack the sensitivity and specificity needed for early diagnosis of cancer [ 27–34 ], which underscores the importance of identifying and validating more sensitive and accurate markers [ 27 ]. It should be noted that side effects from amantadine ingestion are highly unlikely since only single doses of amantadine are administered.…”

Evaluation and Validation of Plasma Proteins Using Two Different Protein Detection Methods for Early Detection of Colorectal Cancer

“…In recent years, several studies have identified blood-based protein marker panels and signatures, for which AUCs higher than 0.8 for were reported for detection of CRC. However, as identified in comprehensive systematic reviews, the participants in these studies were mostly recruited in clinical settings [15,16,21]. Two previous studies from our group had identified eight- and six-marker panels with AUCs for CRC of 0.76 [13] and 0.84 [22], respectively.…”

“…Several blood-based protein marker signatures have been identified in previous years but only very few studies validated the signatures in an independent validation set and, so far, no study has repeated protein measurements in the same set of samples with different protein detection methods [15,16]. Hence, the current study was performed with an objective to evaluate and validate a protein biomarker signature for CRC early detection in a three-stage design.…”