Prognostic value of Osteopontin (SPP1) in colorectal carcinoma requires a personalized molecular approach

Abstract

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade ( p = 0.008), tumor invasion ( p = 0.01), and distant metastasis ( p = 0.04). Kaplan–Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression ( p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker ( p = 0.02). However, nuclear SPP1 expression did not show any prognostic value ( p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes’ assessment is highly recommended toward precision oncology.

The Crucial Role of CXCL8 and Its Receptors in Colorectal Liver Metastasis

“…Osteopontin (OPN) is widely distributed in various tissues and cells and is involved in tissue repair, self-metabolism, and other functions that allow OPN to play an important role in tumor metastasis [44–46]. Presently, it has been shown that OPN is related to both the EMT and MET processes of tumor cells.…”

Analysis of Expression and Its Clinical Significance of the Secreted Phosphoprotein 1 in Lung Adenocarcinoma

“…In multiple malignant tumors such as gastric, esophageal, and colorectal cancers, SPP1 could be detected to have a significantly high expression. Moreover, the SPP1 expression level was significantly higher in tumors with higher malignancy than that in tumors with lower malignancy (Lin et al, 2015;Xu et al, 2017;Chen et al, 2018;Assidi et al, 2019). Xu et al (2017) found that SPP1 could activate the epithelial-mesenchymal transition (EMT) pathway to promote the metastasis of colorectal cancer.…”

Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients

“…In the immune-risk model, secreted phosphoprotein 1 (SPP1 or OPN) is a widely studied signature in tumors, which is normally involved in the process of osteoclasts' attachment to mineralized bone matrix. It is elevated in tumors for progression and metastasis, and its alternatively spliced variants are related to many malignant traits in cancers, such as epithelial-mesenchymal plasticity, cancer cell stemness, chemoresistance, and radioresistance [15][16][17][18][19][20]. However, the variants of SPP1 due to aberrantly processing may cause autoimmune reactions in tumors, which can lead to better outcomes in partial patients [21,22].…”