KRT7 Overexpression is Associated with Poor Prognosis and Immune Cell Infiltration in Patients with Pancreatic Adenocarcinoma

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is a deadly tumor with a high recurrence rate and poor prognosis. Keratin 7 (KRT7) is a member of the keratin gene family that is involved in the regulation of cell growth, migration and apoptosis in many cancers. However, the role of KRT7 and its biological functions in PAAD remain unclear. We systemically analyzed the expression and clinical values of KRT7 in PAAD. Methods: The Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Human Protein Atlas (HPA) databases were used to analyze the mRNA and protein expression of KRT7 in PAAD. The prognosis and subgroup analysis of KRT7 in PAAD patients was performed using the GEPIA, PROGgeneV2 and UALCAN databases. Later, the correlation between KRT7 expression and tumor immune molecules in PAAD was evaluated using the Immune Cell Abundance Identifier (ImmuCellAI) and TISIDB databases. Finally, the functional enrichment pathway of KRT7 and its coexpressed genes were analyzed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape databases and Gene Set Enrichment Analysis (GSEA). Results: The mRNA and protein expression of KRT7 was increased in PAAD tissues compared with normal tissues. High KRT7 expression was closely associated with tumor grade, TP53 mutations and poor prognosis in PAAD patients. Cox regression analysis proved that overexpressed KRT7 was an important and independent risk factor for poor overall survival (P = 0.006, HR =1.87) and disease-free survival (P = 0.019, HR =1.793) in PAAD. Additionally, KRT7 expression was significantly associated with immune infiltration of tumor immune cells and immunomodulators. Functional enrichment analyses and GSEA indicated that KRT7 might be involved in the regulation of the p53 pathway in PAAD. Conclusion: Overexpressed KRT7 could be a promising prognostic and therapeutic target biomarker for PAAD by bioinformatics analysis.

Transcriptionally defined morphological subtypes of pancreatic ductal adenocarcinoma

“…Another large cluster comprised cells with high expression of the carcinoembryonic antigen-related cell adhesion molecules CEACAM5 and CEACAM6 , which mediate cell adhesion and promote tumour invasion 38 , as well as MUCL3 , which has been shown to enhance PDAC cell proliferation, migration and invasion 39 ; this was labelled Classical_invasive . A smaller cluster defined by high expression of KRT7 , an intermediate filament protein known to be overexpressed in pancreatic cancer tissues compared to non-malignant pancreatic tissue 40 , was labelled Classical_adverse since a correlation of KRT7 overexpression with poorer overall survival of PDAC patients has been suggested 41 . Finally, the smallest cluster comprised cells highly expressing regenerating family member 4 ( REG4 ), which is thought to play a role in carcinoma development from intestinal-type intraductal papillary mucinous neoplasms (IPMNs) 42 .…”

“…Of these, clusters 3, 8, 9, 11, 13, were enriched for ‘basal-like’ marker gene expression and were therefore summarised as ‘Basal-like’. Among the ‘classical’ clusters, clusters 0 and 4 shared enrichment for invasion related genes such as CEACAM5 and CEACAM6 and were summarised as Classical_invasive; clusters 2, 5, 6, 10, 12, 14, shared expression of secretion related genes such as TFF1, TFF2 and OLFM4 and were therefore summarised as Classical_secretory ; cluster 1 did not show secretory features but high expression of KRT7 , associated with poorer outcome in PDAC 41 , and was therefore labelled Classical_adverse; and the REG4-expressing cluster 7 was labelled Classical_REG4 . Cell clusters and gene expression are visualised on the same UMAP representation as in Figure 2A.…”

High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality

“…Moreover, high levels of either WISP1 or CD73 were correlated with the density of immunosuppressive CD8+ T cells [ 34 , 35 , 38 ], thus leading to PC growth, metastasis, and disease progression [ 34 ]. Expression of KRT7 has been significantly associated with immune infiltration of tumor immune cells and immunomodulators in other carcinomas [ 39 ]. Thus, KRT7-positive benign epithelial cells surrounding prostate tumors may be also involved in functional interactions with immune cells.…”

“…Roles have been described for keratins other than KRT7 in the immune system and inflammation, DNA damage response and resistance to apoptosis, or apico-basal polarization [ 55 , 56 ]. Functional enrichment analyses and GSEA indicated that KRT7 might be involved in the regulation of the p53 pathway in pancreatic adenocarcinoma [ 39 ]. KRT7 was also positively correlated with keratin-8 (KRT8) expression in an intra-cellular gene-gene correlation, with KRT8 having been identified as a pan-cancer early biomarker in a multi-scale integrated analysis [ 57 ].…”

Robust Prognostic Subtyping of Muscle-Invasive Bladder Cancer Revealed by Deep Learning-Based Multi-Omics Data Integration

“…KRT7 is a member of the keratin gene family and is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. KRT7 was reported as a predictive factor of various types of cancer, such as colorectal cancer ( 41) and renal clear cell carcinoma (42), but bad prognostic factor in esophageal squamous cell carcinoma (43) and pancreatic adenocarcinoma (44). KRT7 was also reported to promote epithelialmesenchymal transition (EMT) of ovarian cancer (45).…”