Emerging Tumor Biomarkers in Pancreatic Cancer and Their Clinical Implications

Abstract

Pancreatic cancer is one of the deadliest malignancies, and this is attributed to the fact that it is diagnosed at a late stage and there are limited treatment options. Tumor biomarkers are used to improve early diagnosis, treatment, and decision-making and to estimate patients' outcomes. This review aims to discuss the new functions of important biomarkers, such as miRNAs, GATA6, L1CAM, and MUC1 in pancreatic cancer. MiRNAs, including miR-21, miR-155, and miR-196a, are prognostic in PC and may be potential therapeutic targets through the regulation of oncogenic pathways and chemoresistance. GATA6, a transcription factor that controls tumor differentiation and immune escape, has been proposed as a pancreatic ductal adenocarcinoma (PDAC) subtyping marker and a predictor of chemotherapy response. L1CAM promotes tumor growth, invasion, and immune suppression, which leads to the formation of new metastases and perineural invasion. MUC1, a glycoprotein with altered glycosylation, is a marker of tumor progression, immune escape, and resistance to chemotherapy. These biomarkers can be combined into diagnostic panels that may increase the accuracy of the diagnosis and help to individualize the treatment plan. However, the present study is inconclusive, and more clinical evidence is needed to apply these biomarkers in clinical practice. More specific research should be directed towards the development of new targeted therapies that would act on these molecular targets and improve the prognosis and treatment of pancreatic cancer.

Keywords: GATA6; L1CAM; MUC1; cancer biomarkers; cancer detection; microRNA; pancreatic cancer.

Figure 1

MicroRNAs’ (miRNA) synthesis and way of action. miRNAs are produced by RNA polymerase II, and miRNAs undergo processing by the Drosha complex to become precursor miRNAs (pre-miRNAs) and are further modified by Dicer in the cytoplasm to form miRNA duplexes. When the miRNA duplex is processed by Dicer, one of the strands is loaded onto the RNA-induced silencing complex (RISC), and the other is removed. The guide strand is retained to direct RISC to the target mRNA through complementary base pairing that occurs mostly at the 3′ untranslated region (UTR). If the miRNA has near-perfect sequence similarity to the target mRNA, AGO proteins in the RISC affect the endonucleolytic cleavage of the mRNA, resulting in its degradation. The cleaved mRNA is then further broken down by exonucleases, thus suppressing gene expression [34,35]. Created with BioRender.com; https://BioRender.com/j34i195 (accessed on 8 February 2025).

Figure 2

The AKT signaling pathway is known to be regulated by miR-21 through the targeting and suppression of the tumor suppressor phosphatase and tensin homolog (PTEN). Normally, PTEN dephosphorylates phosphatidylinositol-3,4,5-triphosphate (PIP3), preventing AKT activation. However, reduced PTEN levels due to miR-21 result in increased PIP3 levels and, thus, sustained phosphorylation and the activation of AKT. This boosts cell survival, proliferation, and apoptosis resistance, all leading to tumor progression. The figure shows how miR-21 affects the PTEN/AKT pathway and its oncogenic role in cancer development [71,72]. Created with BioRender.com; https://BioRender.com/f76q527 (accessed on 8 February 2025).

Figure 3

MiR-21 modulates the MAPK/MEK/ERK signaling pathway directly by downregulating the SPRY and DUSPs that normally suppress ERK activation. MiR-21 facilitates sustained MEK ERK phosphorylation by suppressing certain inhibitors, thereby enhancing cell proliferation and survival. Dysregulation fuels unchecked growth in tumor cells, fostering resistance in apoptosis that occurs sporadically amidst rapid proliferation. The figure illustrates the role of miR-21 in modulating the MAPK/MEK/ERK pathway, emphasizing its deep oncogenic influence in cancer development processes [73,74,75,76]. Created with BioRender.com; https://BioRender.com/e16k991 (accessed on 8 February 2025).