Circulating
tumor-related materials (CTRMs) shed from original
or metastatic tumors, carry a lot of tumor information and are considered
as important markers for cancer diagnosis and metastasis prognosis.
Herein, we report a colorimetric detection strategy for CTRMs based
on aptamer-based magnetic isolation and endogenous alkaline phosphatase
(AP)-signal amplification. This strategy exhibited high sensitivity
and selectivity toward the CTRMs that express AP heterodimers (the
target of aptamer, a potential tumor marker). For clinical samples,
this CTRM assay significantly discriminated colorectal cancer patients
(n = 50) from healthy individuals (n = 39, p < 0.0001). The receiver operating characteristic
(ROC) analysis indicated the sensitivity and specificity reached 92%
and 82%, respectively, at the optimal cutoff point, the area under
the curve of ROC reached 0.93, suggesting great potential for colorectal
cancer diagnosis and therapeutic monitoring. Compared with CTC assays,
this strategy is simple and has the potential for point-of-care testing.
Cell-SELEX is a powerful tool to generate aptamers that
specifically
bind the native molecules on living cells. Here, we report an aptamer
ZAJ4a generated by cell-SELEX. The molecular target of ZAJ4a was pulled
down by the enriched cell-SELEX pool and identified to be the receptor-type
tyrosine-protein phosphatase F (PTPRF) through a stable isotope labeling
using amino acids in cell culture (SILAC)-based quantitative proteomic
method. ZAJ4a showed high binding affinity with nanomolar range to
cancer cells expressing PTPRF. Meanwhile, PTPRF was proven to highly
express on several cancer cell lines using ZAJ4a as a molecular probe
and to highly express in many kinds of cancer samples using gene expression
profiling interactive analysis (GEPIA2) from the TCGA and GTEx databases.
These results indicate that the aptamer generated by cell-SELEX showed
good specificity at the molecular level. This cell-SELEX and target
identification strategies show great potential for identifying biomarkers
on the cell surface.
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