Keratin 8 Is an Inflammation-Induced and Prognosis-Related Marker for Pancreatic Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the highest-grade malignancies in the world. More effective biomarkers and treatment plans are necessary to improve the diagnosis rate and clinical outcome. The oncogenesis of PDAC is influenced by several factors, including chronic pancreatitis (CP). Keratin 8 (KRT8) is an important member of the keratin protein family and plays a role in regulating the cellular response to stress stimuli and mediating inflammatory reactions. However, the role of KRT8 in pancreatitis and PDAC is still poorly understood. Here we assessed the differentially expressed genes (DEGs) by bioinformatic methods with expression profiles available online for a caerulein-induced mouse model and human PDAC tissue. The prognostic value was evaluated by Kaplan–Meier analysis and Cox regression analysis. The diagnostic value was evaluated by Receiver Operating Characteristic analysis (ROC). The function of the genes was predicted by protein-protein interaction analysis, correlation analysis, and GO analysis. The conclusion was further validated in rat pancreatitis model, human tissue, and PDAC cell lines, including immunohistochemical staining (IHC), CCK-8 assay, wound healing assay, and flow cytometry. KRT8 was found to be upregulated in murine pancreatitis tissue, human CP tissue, and human PDAC tissue. High expression of KRT8 had a negative impact on the prognosis of PDAC patients. KRT8 was predicted to be involved in the regulation of the migration and viability of PDAC cells, which was validated in PDAC cell lines. Knockdown of KRT8 impaired the migration and proliferation and induced apoptosis in PDAC cell lines. In conclusion, keratin 8 is an inflammation-induced molecule and could serve as a diagnostic and prognostic marker for PDAC patients. More studies are needed for further validation from the perspective of precision and individualized medicine.

Identification of the prognosis value of pyroptosis related genes in the NSCLC

“…Among these genes, YWAHZ and BIRC3 were most heavily weighted in the hazard model. It was suggested that overexpression of YWAHZ and BIRC3 could inhibit the pyroptosis [20,21] . Pyroptosis is a pro-in ammatory cell death, which could be triggered by proin ammatory factors, including Interleukin-1β (IL-1β),IL-6 [22] .During pyroptosis process, the GSDMD was cleaved by the in ammatory caspases in the tumor, which played important roles in the pyroptosis [23] .…”

Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

“…For example, a combination of CA19-9 with serum mucin 5AC, a heavily glycosylated protein of the mucin family, improves both sensitivity (73.8%) and specificity (88.6%) as well as the AUC (0.894; 95%CI: 0.844-0.943) for PC diagnosis in patients, better than the values of each individual marker[ 75 ]. There are many other serum markers that can be used for PC or PDAC diagnosis, including macrophage inhibitory cytokine-1[ 76 ], keratin 8[ 77 ], protein induced by vitamin K absence II[ 78 ], and gremlin 1 (GREM1)[ 79 ] (Table 1 ). Meanwhile, combining different markers in a panel could increase the values of sensitivity, specificity, and AUC.…”