Systematic review of blood diagnostic markers in colorectal cancer

Abstract

The purpose of this systematic review was to compare the diagnostic ability of blood markers for colorectal cancer (CRC). A systematic review of the literature for diagnostic blood markers for primary human colorectal cancer over the last 5 years was performed. The primary outcome was to assess the diagnostic ability of these markers in diagnosing colorectal cancer. The secondary outcome was to see whether the marker was compared to other markers. The tertiary outcome was to assess diagnostic ability in early versus late CRC, including stage IV disease. We identified 51 studies (29 prospective, 14 retrospective, and 8 meta-analyses). The markers were divided in broadly four groups: nucleic acids (RNA/DNA/messenger RNA/microRNAs), cytokines, antibodies, and proteins. The most promising circulating markers identified among the nucleid acids were NEAT_v2 non-coding RNA, SDC2 methylated DNA, and SEPT9 methylated DNA. The most promising cytokine to detect CRC was interleukin 8, and the most promising circulating proteins were CA11-19 glycoprotein and DC-SIGN/DC-SIGNR. Sensitivities of these markers for detecting primary colorectal carcinoma ranged from 70 to 98% and specificities from 84 to 98.7%. The best studied blood marker was SEPT9 methylated DNA, which showed great variability with sensitivities ranging from 48.2 to 95.6% and specificities from 80 to 98.9%, making its clinical applicability challenging. If combined with fecal immunochemical test (FIT), the sensitivity improved from 78 to 94% in detecting CRC. Methylated SEPT9, methylated SDC2, and -SIGN/DC-SIGNR protein had better sensitivity and specificity than CEA or CA 19-9. With the exception of SEPT9 which is currently being implemented as a screening test for CRC all other markers lacked reproducibility and standardization and were studied in relatively small population samples.

Upregulation of microRNA‑31 is associated with poor prognosis in patients with advanced colorectal cancer

“…The cluster analysis revealed that only miR-31 was significantly upregulated in non-MSI CRC specimens with the BRAF V600E mutation (sample Id, 341), while miR-429, -375, -200a, -200b and -192 were downregulated compared with that in the other CRC phenotypes, such as CRCs with wild-type BRAF. Generally, molecules that are significantly and specifically upregulated in tumors are useful for screening those tumors via liquid biopsy or other screening tools (26). Therefore, subsequent analyses focused on miR-31 as a candidate prognostic biomarker in the present study.…”

“…microRNAs (miRNA/miR) have been revealed as candidates in tumor progression in various cancer types, and changes in their expression levels are consequently being investigated with the purpose of identifying clinical biomarkers (3)(4)(5)(6)(7)(8)(9). miRNAs constitute a class of small, non-coding RNA molecules, [18][19][20][21][22][23][24][25][26][27] nucleotides in length that function as post-transcriptional regulators of gene expression, either serving as oncogenes or tumor suppressor genes (10,11). In CRC, several miRNAs are aberrantly expressed and target genes downstream of epidermal growth factor receptor (EGFR) signaling; for example, miR-143 and -145 target KRAS and BRAF proteins, respectively (12).…”

Long non‑coding RNA NKILA serves as a biomarker in the early diagnosis and prognosis of patients with colorectal cancer

“…Ideally, this aim can be achieved with a noninvasive and inexpensive method, using readily available biological samples, including serum and feces (37). At present, potential molecular biomarkers for CRC diagnosis are broadly divided into the following four groups: Nucleic acids, cytokines, antibodies and proteins (38). Blood-based markers in current use, including CEA and CA19-9, are suitable for surveillance and for monitoring responses to treatment; however, they exhibit low sensitivity and specificity, ranging between 40 and 70%, and 73 and 90%, respectively, which makes them unsuitable as screening or diagnostic markers (39).…”

Electrochemical Biosensors for Determination of Colorectal Tumor Biomarkers

“…In this sense, the in vitro diagnostic (IVD) of tumor markers is the focal point of research in cancer detection. From the first genetic model of colorectal tumorigenesis proposed by Fearon and Vogelstein in 1990 [2] until today, when it is known that the transformation of adenoma to carcinoma is driven not only by genetic alteration but epigenetic alterations [3], many tumor markers have been proposed to describe this complex process [4][5][6][7][8][9][10][11]. The most recent findings regarding molecular events along the adenoma-carcinoma sequence urgently demand the development of detection methodologies and strategies that allow the simultaneous determination of tumor markers of different molecular nature with simple protocols and suitable for point-of-care (POC) testing.…”