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.
Highlights
Prognosis in different tumours, such as ovarian cancer, melanoma, hepatocellular, breast and gastric carcinomas[17,18,19]
The diagnostic performance of serum nucleoside diphosphate kinase A (NDKA) for the detection of Colorectal cancer (CRC) in this case-control cohort resulted in an AUC of 0.731
In relation to tumour characteristics including tumour stage, invasion of the tumour, lymph node affectation, distant metastasis, differentiation grade or location, no differences were found in the serum NDKA concentration (Supplementary Table S1)
Summary
Prognosis in different tumours, such as ovarian cancer, melanoma, hepatocellular, breast and gastric carcinomas[17,18,19]. High levels of serum NDKA have been reported in individuals with haematological cancers like leukaemia and lymphoma compared with healthy controls, proposing this molecule as a prognostic factor[20,21]. In the case of CRC, several studies have reported significantly higher NDKA protein and/or mRNA expression in tumour tissue in comparison to normal mucosa[23,24,25,26,27,28]. Our group identified through a proteomic study the NDKA, observing increased protein levels in tumour tissue compared to healthy mucosa. We detected by Western blot an increased amount of NDKA in serum of CRC patients, suggesting the potential use of this molecule as a CRC serum marker[29]. NDKA was compared to FIT in terms of diagnostic performance
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