Abstract

Malignant tumor represents a major reason for death in the world and its incidence is growing rapidly. Developing the tools for early diagnosis is possibly a promising way to offer diverse therapeutic options and promote the survival chance. Secreted phosphoprotein 1 (SPP1), also called Osteopontin (OPN), has been demonstrated overexpressed in many cancers. However, the specific role of SPP1 in prognosis, gene mutations, and changes in gene and miRNA expression in human cancers is unclear. In this report, we found SPP1 expression was higher in most of the human cancers. Based on Kaplan-Meier plotter and the PrognoScan database, we found high SPP1 expression was significantly correlated with poor survival in various cancers. Using a large dataset of colon adenocarcinoma (COAD), head and neck cancer (HNSC), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, this study identified 22 common genes and 2 common miRNAs. GO, and KEGG paths analyses suggested that SPP1 correlated genes were mainly involved in positive regulation of immune cell activation and infiltration. SPP1-associated genes and miRNAs regulatory networks suggested that their interactions may play a role in the progression of four selected cancers. SPP1 showed significant positive correlation with the immunocyte and immune marker sets infiltrating degrees. All of these data provide strong evidence that SPP1 may promote tumor progress through interacting with carcinogenic genes and facilitating immune cells’ infiltration in COAD, HNSC, LUAD, and LUSC.

Highlights

  • Malignant tumor represents the primary reason for deaths in the world and its incidence is growing rapidly (Bray et al, 2018)

  • The different Secreted phosphoprotein 1 (SPP1) expression in cancer compared with noncarcinoma tissues was found by the box plots (Figure 1B), and the different expression levels were statistically significant upon Wilcoxon test

  • The SPP1 level apparently increased in cholangiocarcinoma (CHOL), breast invasive carcinoma (BRCA), bladder urothelial carcinoma (BLCA), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), HNSC, liver hepatocellular carcinoma (LIHC), kidney renal papillary cell carcinoma (KIRP), lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), rectum adenocarcinoma (READ), prostate adenocarcinoma (PRAD), thyroid carcinoma (THCA), uterine corpus endometrial carcinoma (UCEC), and stomach adenocarcinoma (STAD), in comparison with the non-carcinoma samples

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Summary

Introduction

Malignant tumor represents the primary reason for deaths in the world and its incidence is growing rapidly (Bray et al, 2018). Lung cancer (LC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), breast cancer (BC), cervical cancer, ovarian cancer, head and neck cancer (HNC), and endometrial cancer stand for the frequently occurring malignant tumors that kill millions of people every year SPP1 is an integrin-binding glyco-phosphoprotein, which shows over-expression in a variety of tumors, such as liver cancer, LC, prostate cancer (PCa), BC, and CRC (Rangaswami et al, 2006; Blasberg et al, 2010; Kahles et al, 2014). Studies have demonstrated that high expression levels of SPP1 is associated with poor prognosis (Wei et al, 2018; Lamort et al, 2019). SPP1 plays a role in many types of cancers, how its expression is regulated in relation to immune infiltration, gene mutation, gene and miRNA levels remains unclear

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