New plasma diagnostic markers for colorectal cancer: transporter fragments of glutamate tRNA origin.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Early diagnosis of the disease can greatly improve the clinical prognosis for patients with CRC. Unfortunately, there are no current simple and effective early diagnostic markers available. The transfer RNA (tRNA)-derived RNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs), which have been shown to play an important role in the development and prognosis of CRC. However, only a few studies on tRFs as early diagnostic markers in CRC have been conducted. In this study, previously ignored tRFs expression data were extracted from six paired small RNA sequencing data in the Sequence Read Archive (SRA) database using MINTmap. Three i-tRFs, derived from the tRNA that transports glutamate (i-tRF-Glu), were identified and used to construct a random forest diagnostic model. The model performance was evaluated using the receiver operating characteristic (ROC) curve and precision-recall (PR) curve. The area under the curves (AUC) for the ROC and PR was 0.941 and 0.944, respectively. We further verified the differences in expression of the these i-tRF-Glu in the tissue and plasma of both CRC patients and healthy subjects using quantitative real-time PCR (qRT-PCR). We found that the ROC-AUC of the three was greater than traditional plasma tumor markers such as CEA and CA199. Our bioinformatics analysis suggested that the these i-tRF-Glu are associated with cancer development and glutamate (Glu)-glutamine (Gln) metabolism. Overall, our study uncovered these i-tRF-Glu that have early diagnostic significance and therapeutic potential for CRC, this warrants further investigation into the diagnostic and therapeutic potential of these i-tRF-Glu in CRC.

Iron metabolism in colorectal cancer.

Iron, as one of the essential trace elements in the human body, is involved in a wide range of critical biochemical reactions and physiological processes, including the maintenance of the normal cell cycle, mitochondrial function, nucleotide metabolism, and immune response. In this context, iron is naturally associated with cancer occurrence. Cellular iron deficiency can induce apoptosis, however, iron can also engage in potentially harmful reactions that produce free radicals because of its capacity to gain and lose electrons. Studies suggest that dietary iron, particularly heme iron, may be one of the leading causes of colorectal cancer (CRC). Moreover, patients with CRC have abnormal iron absorption, storage, utilization, and exportation. Therefore, iron is crucial for the development and progression of CRC. Elaborating on the alterations in iron metabolism during the onset and advancement of CRC would help to further explain the role and mechanism of iron inside the body. Thus, we reviewed the alterations in numerous iron metabolism-related molecules and their roles in CRC, which may provide new clues between iron metabolism and CRC.