Abstract
Cancer is becoming the leading cause of death and a major public health problem. Although many advanced treatment strategies are currently in use, the general prognosis of cancer patients remains dismal due to the high frequency of recurrence, metastasis. The identification of effective biomarkers is important for predicting survival of cancer patients and improving treatment efficacy. In this study, we comprehensively analyzed WNT1-inducible-signaling pathway protein 1 (WISP1) expression and explored its correlation with prognosis in pan-cancer using tumor IMmune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). We also examined correlations between WISP1 and immunocyte infiltration using TIMER. We identified genes co-expressed with WISP1 using the LinkedOmics database and analyzed associated gene ontology using Metascape. Finally, we constructed protein-protein interaction networks and examined correlations between genes co-expressed with WISP1 and immunocyte infiltration in pan-cancer. WISP1 level differed between human pan-cancer tissues and normal tissues, indicating its potential as a prognostic biomarker. WISP1 expression was correlated with tumor purity and immunocyte infiltration, especially monocyte-macrophage trafficking and M2 polarization. Genes co-expressed with WISP1 were mainly associated with extracellular matrix organization, with collagen members COL6A3, COL5A1, and COL8A1 being key genes correlated with macrophage infiltration and M2 polarization in pan-cancer. Conversely, in certain types of cancer with better prognoses, WISP1 was associated with low M2 macrophage infiltration. These results suggest that WISP1 affect clinical prognosis through associations with tumor purity, immune cell infiltration, and macrophage M2 polarization in pan-cancer, with collagen member proteins may serving as effector molecules of WISP1.
Highlights
According to estimates from the World Health Organization (WHO) in 2015, cancer is the first or second leading cause of death, with increasing incidence and mortality (Bray et al, 2018)
Our findings suggest that WNT1-induciblesignaling pathway protein 1 (WISP1) affects clinical prognosis through associations with tumor purity, immune cell infiltration, and macrophage M2 polarization in pan-cancer, with collagen member proteins most likely serving as WISP1 effector molecules
Patients in the WISP1-high group had shorter recurrence-free survival (RFS) than those in the WISP1-low group for CESC (HR = 4.28, p = 0.0000), kidney renal papillary cell carcinoma (KIRP) (HR = 3.35, p = 0.0180), lung adenocarcinoma (LUAD) (HR = 1.7, p = 0.0300), PAAD (HR = 3.5, p = 0.0090), SARC (HR = 1.78, p = 0.0190), and THCA (HR = 2.14, p = 0.0500; Supplementary Figure S1). These findings indicate that WISP1 expression is elevated in most types of human cancer, indicating that it most likely serve as a biomarker for poor prognosis
Summary
According to estimates from the World Health Organization (WHO) in 2015, cancer is the first or second leading cause of death, with increasing incidence and mortality (Bray et al, 2018). CCN family proteins have highly conserved biological structures, and many studies have described the effects of pathological events in each CCN catalytic domain on cell differentiation (Nishida et al, 2015), migration (Li et al, 2015), mitogenesis (Weiskirchen, 2011), chemotaxis (Zarogoulidis et al, 2015), and angiogenesis (Tsai et al, 2017). These proteins have different expression levels and play variable roles in the biology of human cancer (Klenotic et al, 2016). The expression and function of WNT1-induciblesignaling pathway protein 1 (WISP1) implicates it as an oncogene, but its expression and physiological roles in diverse cancer types remain unclear
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