PRR11 unveiled as a top candidate biomarker within the RBM3‐regulated transcriptome in pancreatic cancer

Abstract

The outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker of disease severity and chemotherapy response in several types of cancer, including pancreatic cancer. The aim of this study was to unearth RBM3-regulated genes and proteins in pancreatic cancer cells in vitro, and to examine their expression and prognostic significance in human tumours. Next-generation RNA sequencing was applied to compare transcriptomes of MIAPaCa-2 cells with and without RBM3 knockdown. The prognostic value of differentially expressed genes (DEGs) was examined in The Cancer Genome Atlas (TCGA). Top deregulated genes were selected for further studies in vitro and for immunohistochemical analysis of corresponding protein expression in tumours from a clinically well-annotated consecutive cohort of 46 patients with resected pancreatic cancer. In total, 19 DEGs (p < 0.01) were revealed, among which some with functions in cell cycle and cell division stood out; PDS5A (PDS cohesin associated factor A) as the top downregulated gene, CCND3 (cyclin D3) as the top upregulated gene, and PRR11 (proline rich 11) as being highly prognostic in TCGA. Silencing of RBM3 in MiaPaCa-2 cells led to congruent alterations of PDS5A, cyclin D3, and PRR11 levels. High protein expression of PRR11 was associated with adverse clinicopathological features and shorter overall survival. Neither PDS5A nor cyclin D3 protein expression was prognostic. This study unveils several RBM3-regulated genes with potential clinical relevance in pancreatic cancer, among which PRR11 shows the most consistent association with disease severity, at both transcriptome and protein levels.

Prognostic value of PRR11 and immune cell infiltration in Ewing sarcoma

“…This is consistent with the previously reported role of PRR11 in non-small cell lung carcinoma [35,37]. Furthermore, PRR11 has been associated with other types of lung cancer [38], clear cell renal cell carcinoma [39], tongue squamous cell carcinoma [40], pancreatic cancer [41], gastric cancer [42], osteosarcoma [43], breast cancer [44], etc. It possibly exerts effects on the cell cycle and autophagy, eventually leading to tumorigenesis, progression, and poor prognosis of patients.…”

RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia

“…However, some studies have shown that overexpression of RBM3 is usually closely related to good clinical prognosis, and even used as a biomarker to evaluate cancer treatment (Al‐Astal et al, 2016). Deletion of RBM3 is associated with a variety of clinically more invasive cancers, and it is an independent factor of poor prognosis (Olsson Hau et al, 2022). High levels of RBM3 in prostate and breast cancer are a good biomarker of a low risk of cancer progression, low recurrence, and optimistic prognosis (Chen, Ikeda, et al, 2019).…”

PRR11 is a prognostic biomarker and correlates with immune infiltrates in bladder urothelial carcinoma

“…The PRR11 gene on chromosome 17q22 encodes a proline-rich protein with a zinc finger domain and a bivalent nuclear localization signal 20 . Since its discovery in 2013, the relationship between this gene and tumors has been getting closer, and reports have revealed that it is related to the poor outcomes of various tumor types 21 , such as ovarian carcinoma 22 , breast cancer 23 , non-small cell lung cancer 24 , colorectal cancer 25 , and pancreatic cancer 26 . In addition, data indicate that it is involved in the epithelial-mesenchymal transition (EMT) process 27 .…”