Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.

Pancreatic cancer is the most lethal type of malignancy and is characterized by high invasiveness without severe symptoms. It is difficult to detect PC at an early stage because of the low diagnostic accuracy of existing routine methods, such as abdominal ultrasound, CT, MRI, and endoscopic ultrasound (EUS). Therefore, it is of value to develop new diagnostic techniques for early detection with high accuracy. In this review, we aim to highlight research progress on novel biomarkers, artificial intelligence, and nanomaterial applications on the diagnostic accuracy of pancreatic cancer. 

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Advances in biomarkers and techniques for pancreatic cancer diagnosis

The incidence and mortality of cancer are increasing each year. At present, the sensitivity and specificity of the blood biomarkers that were used in clinical practice are low, which make the detection rate of cancer decrease. With advances in bioinformatics and technology, some non-coding RNA as biomarkers can be easily detected through some traditional and new technologies. Circular RNAs (circRNAs) are non-coding RNAs, that is, they do not encode proteins, and have important regulatory functions. CircRNAs can remain stable in bodily fluids, such as in saliva, blood, urine, and especially plasma. The difference in the expression of plasma circRNAs between cancer patients and normal people may suggest that plasma circRNAs may play an important role in the occurrence and development of cancer. In this review, we summarized the clinical effect of plasma circRNAs in several high-incidence cancers. CircRNAs may be effective biomarkers for tumour diagnosis, treatment selection and prognosis evaluation.

/pdf/plasma-circrnas-as-biomarkers-in-cancer-10v8gjwvwk.pdf

Plasma circRNAs as Biomarkers in Cancer.

Pancreatic cancer is an aggressive malignance with high mortality. The lack of early diagnosis and effective therapy contributes to the high mortality of this deadly disease. For a long time being, the alterations in coding RNAs have been considered as major targets for diagnosis and treatment of pancreatic cancer. However, with the advances in high-throughput next generation of sequencing more alterations in non-coding RNAs (ncRNAs) have been discovered in different cancers. Further mechanistic studies have demonstrated that ncRNAs such as long noncoding RNAs (lncRNA), circular RNAs (circRNA) and piwi-interacting RNA (piRNA) play vital roles in the regulation of tumorigenesis, tumor progression and prognosis. In recent years, increasing studies have focused on the roles of ncRNAs in the development and progression of pancreatic cancer. Novel findings have demonstrated that lncRNA, circRNA, and piRNA are critically involved in the regulation of gene expression and cellular signal transduction in pancreatic cancer. In this review, we summarize the current knowledge of roles of lncRNA, circRNA, and piRNA in the diagnosis and prognosis of pancreatic cancer, and molecular mechanisms underlying the regulation of these ncRNAs and related signaling in pancreatic cancer therapy. The information provided here will help to find new strategies for better treatment of pancreatic cancer.

Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs.

Pancreatic cancer (PC) is a kind of common digestive system cancer with the worst prognosis for its insidious symptoms and high invasiveness. Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed circular structure, which are more stable and conservative than linear RNAs and process major functions of microRNA (miRNA) sponge, RNA binding protein (RBP) sponge and polypeptide translation template. Incremental researches have proved that circRNAs express aberrantly and play a vital role in various types of cancer. Hence, we reviewed the biogenesis, degradation, characteristics, and biological functions of circRNAs and summarized the roles circRNAs played in the proliferation, invasion, metastasis, chemoresistance and exosome-mediated intercellular communication of PC. We then summed up a workflow regarding circRNA research in cancer and relative specific databases and experimental methods. In the future, more efforts ought to be put into circRNAs research in PC, including basic research of discovering and testifying circRNAs centered ceRNA networks, and clinical research of exploiting exosomal or circulating circRNAs as a diagnostic biomarker, chemotherapy sensitivity predictor and prognostic predictor.

Mobius strip in pancreatic cancer: biogenesis, function and clinical significance of circular RNAs

Emerging evidence has shown that circular RNAs (circRNAs) serve as a promising biomarker in different malignancies. Specifically, circ_001569 has been found to be upregulated in some types of human gastrointestinal cancer. In this study, we aimed to investigate clinical significances, diagnostic and prognostic values of circ_001569 in pancreatic cancer (PC), and identify its effects on the malignant behaviors of PC cells. The expression of circ_001569 was determined in 26 tissues samples and 97 plasma samples from PC patients by qRT-PCR. Relationship between circ_001569 expression and clinicopathological parameters was analyzed by Chi-square test. Diagnostic and prognostic values of circ_001569 were evaluated by ROC curves, Kaplan-Meier curves, and Cox regression analysis. The effects of circ_001569 on the proliferation, migration, invasion, and apoptosis of PC cells were assessed by MTT, wound healing, Transwell invasion assays, and flow cytometric analysis, respectively. Results showed that the expression of circ_001569 was upregulated in tissues and plasma of PC patients. High circ_001569 level was positively correlated with lymphatic metastasis, clinical stage, and venous invasion. Circ_001569 level was an independent prognostic indicator for overall survival rates of PC patients, and patients with high circ_001569 level had a poor prognosis. The AUC of circ_001569 was 0.716 (95% CI: 0.642-0.790) with a sensitivity and specificity of 62.76% and 74.29%, respectively. In vitro, circ_001569 silencing decreased cell proliferation, migration, and invasion, but promoted cell apoptosis of PC cells. Our data demonstrate that high circ_001569 level associates with tumor malignant behaviors, and may serve as a potential biomarker in the diagnosis and prognosis of PC.

https://journals.sagepub.com/doi/pdf/10.1177/1533033820983302

Identification of Circ_001569 as a Potential Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer.

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Identification of Circ_001569 as a Potential Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer.