Evaluation of serum nucleoside diphosphate kinase A for the detection of colorectal cancer

Abstract

We previously described the over-expression of nucleoside diphosphate kinase A (NDKA) in tumours and serum from colorectal cancer (CRC) patients, suggesting its use as biomarker. In this study we evaluated the diagnostic accuracy of serum NDKA to detect advanced neoplasia (CRC or advanced adenomas). Furthermore, the performance of NDKA was compared with the faecal immunochemical test (FIT). The study population included a case-control cohort and a screening cohort (511 asymptomatic first-degree relatives of CRC patients that underwent a colonoscopy and a FIT). Serum NDKA was elevated in CRC patients in the case-control cohort (p = 0.002). In the screening cohort, NDKA levels were higher for advanced adenomas (p = 0.010) and advanced neoplasia (p = 0.006) compared to no neoplasia. Moreover, elevated NDKA was associated with severe characteristics of adenomas (≥3 lesions, size ≥ 1 cm or villous component). Setting specificity to 85%, NDKA showed a sensitivity of 30.19% and 29.82% for advanced adenomas and advanced neoplasia, respectively. NDKA combined with FIT (100 ng/mL cut-off) detected advanced adenomas and advanced neoplasia with 45.28% and 49.12% sensitivity, with specificity close to 90%. The combination of serum NDKA and FIT can improve the detection of advanced neoplasia, mainly for lesions located on the proximal colon, in asymptomatic individuals with CRC family-risk.

Fecal immunochemical tests in combination with blood tests for colorectal cancer and advanced adenoma detection—systematic review

“…Figure 1 shows the study selection process. Of 2054 unique articles, 26 were given full text assessment and eight of them were included in our systematic review 13–20 . The 18 articles excluded after full‐text review did not report sensitivities and specificities for FIT combined with a blood test.…”

“…Two authors (TN and KW) independently extracted data on study characteristics and outcomes from relevant articles 13–20 . Eventual discrepancies were resolved by consensus.…”

“…Two authors (TN and KW) independently extracted data on study characteristics and outcomes from relevant articles. [13][14][15][16][17][18][19][20] Eventual discrepancies were resolved by consensus. Sensitivities were extracted separately for CRC and AA.…”

“…Conducted solely in a screening setting (16) Conducted in a screening setting, but additional inclusion of clinically detected CRC cases (13,14) Conducted in asymptomatic firstdegree relatives of CRC patients (19,20) Comprising controls and symptomatic cases (15,18) Symptomatic cohort (17) focused on individuals aged 50 14,16 or 55 13 and older, whereas the other studies either included younger participants 15,17,19,20 or did not report an age range. 18 All studies examining AAs defined them as adenomas matching at least one of the following criteria: size !1 cm, high-grade dysplasia, adenomas with villous components.…”

Extracellular Vesicle-Mediated Purinergic Signaling Contributes to Host Microenvironment Plasticity and Metastasis in Triple Negative Breast Cancer

“…Investigations by our lab and others into extracellular Nm23 illuminate a diverging plotline for its role in oncogenesis. Among these, elevated Nm23 expression was reported in sera of patients with breast cancer [31] , colorectal cancer [38,39] , neuroblastoma [40] , renal carcinoma [41] , and hematological malignancies [42] . Metastatic breast cancer cells of human and murine origin secrete elevated levels of NDPK-A and -B isoforms compared to non-tumorigenic breast cells, suggesting a functional role for secreted NDPK in metastasis [43,44] .…”