Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide and a longstanding critical challenge for public health. Screening has been suggested to effectively reduce both the incidence and mortality of CRC. However, the drawback of the current screening modalities, both stool-based tests and colonoscopies, is limited screening adherence, which reduces the effectiveness of CRC screening. Blood tests are more acceptable than stool tests or colonoscopy as a first-line screening approach. Therefore, identifying blood biomarkers for detecting CRC and its precancerous neoplasms is urgently needed to fulfill the unmet clinical need. Currently, many kinds of blood contents, such as circulating tumor cells, circulating tumor nucleic acids, and extracellular vesicles, have been investigated as biomarkers for CRC detection. Among these, small extracellular vesicles (sEVs) have been demonstrated to detect CRC effectively in recent reports. sEVs enable intercellular shuttling—for instance, trafficking between recipient cancer cells and stromal cells—which can affect tumor initiation, proliferation, angiogenesis, immune regulation; metastasis, the cancer-specific molecules, such as proteins, microRNAs, long noncoding RNAs, and circular RNAs, loaded into cancer-derived sEVs may serve as biomarkers for the detection of cancers, including CRC. Indeed, accumulating evidence has shown that nucleic acids and proteins contained in CRC-derived sEVs are effective as blood biomarkers for CRC detection. However, investigations of the performance of sEVs for diagnosing CRC in clinical trials remains limited. Thus, the effectiveness of sEV biomarkers for diagnosing CRC needs further validation in clinical trials.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide
Cancer-specific molecules, such as proteins, microRNAs, long noncoding RNAs, and circular RNAs, loaded into cancer-derived small extracellular vesicles (sEVs) may serve as biomarkers for the detection of cancers, including CRC
In CRC, sEVs derived from cancer-associated fibroblasts (CAFs) have been shown to prime cancer stem cells and contribute to chemoresistance through Wnt signaling [16]
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide. To face the challenge posed by the current CRC prevalence, nationwide screening programs have been implemented worldwide. In CRC, sEVs derived from cancer-associated fibroblasts (CAFs) have been shown to prime cancer stem cells and contribute to chemoresistance through Wnt signaling [16]. These studies indicated the essential role of sEVs in intercellular communication during cancer progression. Overexpression of CAF-derived sEV-miR-92a-3p downregulates the expression of its target genes FBXW7 (F-box and WD repeat domain containing 7) and MOAP1 (modulator of apoptosis 1) to inhibit the ubiquitination and degradation of β-catenin, resulting in the invasion and migration of CRC cells via activation of the Wnt-β-catenin signaling pathway [21]. An increasing number of studies are finding that sEV-derived molecules, such as lncRNAs and circRNAs, are involved in specific signaling axes to alter tumor metastasis [22–24]
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