Abnormal CBLL1 mRNA expression in pan-cancerous tissues
In the UCSC database, we found abnormal expression of CBLL1 in a variety of tumors (Fig. 1 and S1). In detail, CBLL1 is highly expressed in Cholangio carcinoma (CHOL), Colon adenocarcinoma (COAD), Esophageal carcinoma (ESCA), Glioblastoma multiforme (GBM), Kidney Chromophobe (KICH), Liver hepatocellular carcinoma (LIHC), Lung squamous cell carcinoma (LUSC), Head and Neck squamous cell carcinoma (HNSC), Rectum adenocarcinoma (READ) and Stomach adenocarcinoma (STAD) tissues (Fig. 1A-J), and poorly expressed in Thyroid carcinoma (THCA) and Uterine Corpus Endometrial Carcinoma (UCEC) tissues (Fig. 1K-L).
The expression of CBLL1 is related to the age, race, clinical stage and therapeutic effect of patients with pan-cancer
After collating and analyzing the clinicopathological features of 33 cancer patients, it was found that the expression level of CBLL1 was correlated with the age of Breast invasive carcinoma (BRCA), CHOL, Kidney renal papillary cell carcinoma (KIRP), LIHC and Pancreatic adenocarcinoma (PAAD) patients (Fig. S2), the expression level of CBLL1 mRNA was correlated with the race of patients with Bladder Urothelial Carcinoma (BLCA), BRCA, GBM, KIRC, LIHC and Thymoma (THYM) (Fig. S3), and the expression level of CBLL1 mRNA was correlated with the clinical stage of patients with ACC, BRCA, KIRC, LIHC, PAAD, STAD, Testicular Germ Cell Tumors (TGCT) and THCA (Fig. 2). The expression level of CBLL1 mRNA was related to the therapeutic effect of patients with BLCA, KIRC, Kidney renal clear cell carcinoma (KIRP), Brain Lower Grade Glioma (LGG), PRAD and UCEC (Fig. S4).
The expression of CBLL1 is related to the prognosis of patients with pan-cancer
Survival analysis of clinical information of 33 kinds of cancer patients showed that the expression level of CBLL1 mRNA was correlated with OS in patients with KIRC (Fig. 3A), the expression level of CBLL1 mRNA was correlated with DSS in patients with KIRC, LUSC, THCA and THYM (Fig. 3B-E), the expression level of CBLL1 mRNA was correlated with DFI in patients with MESO, PRAD and STAD (Fig. 3F-H), and the expression level of CBLL1 mRNA was correlated with PFI in patients with KIRC, PRAD and UVM (Fig. 3I-K). Univariate COX regression analysis found that CBLL1 mRNA expression level was a risk factor for OS in patients with KICH, KIRC, LAML and THYM (Fig. 4A);DSS in patients with KIRC, PCPG and THYM (Fig. 4B); DFI in patients with OV, PRAD and STAD (Fig. 4C); PFI in patients with GBM, KIRC, Ovarian serous cystadenocarcinoma (OV), THYM and UVM (Fig. 4D).
The expression level of CBLL1 is associated with TMB and MSI in patients with pan-cancer
The mutation load of pan-cancer tumor was calculated based on the expression data of pan-cancer mRNA in UCSC database, and the correlation between the expression level of CBLL1 mRNA and TMB of pan-cancer patients was analyzed. In other words, the expression level of CBLL1 mRNA was correlated with TMB in patients with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM (Fig. 5A and Table 1); The expression level of CBLL1 mRNA was correlated with MSI in patients with pan-cancer. In detail, the expression level of CBLL1 mRNA was associated with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and MSI in patients with UCEC (Fig. 5B and Table 2).
The expression level of CBLL1 mRNA is related to the microenvironment of pan-cancer
The expression level of CBLL1 mRNA was correlated with tumor microenvironment (Fig. 6 and Table 3). Figure 6 shows the correlation between CBLL1 mRNA expression level and tumor stromal cells via P values. In detail, the expression level of CBLL1 was correlated with tumor stromal cells such as TGCT, LGG, SARC, GBM, LUSC, BLCA, BRCA, THCA, PCPG and so on (Fig. 6 and Table 3). Figure S5 shows the correlation between CBLL1 mRNA expression level and tumor immune cells via P values. In detail, the expression level of CBLL1 was correlated with tumor immune cells such as BRCA, LGG, THCA, GBM, LUSC, SARC, UCEC, PCPG, LIHC, etc (Fig. S5 and Table 3).
The expression level of CBLL1 is related to the immune cells of pan-cancerous tumors
Figure 7 and S6 show the correlation between the expression level of CBLL1 mRNA and the tumor immune infiltrating cells with the lowest P value. The expression level of CBLL1 is correlated with BLCA (T cells follicular helper), BRCA (Tcells CD4 memory resting), COAD (B cells memory), GBM (T cells gamma delta), HNSC (B cell snaive), KICH (T cells CD4 memory resting), KIRC (T cells regulatory,Tregs), LAML (Monocytes), LIHC (T cells CD8), LUAD (T cells CD4 memory activated), LUSC (Neutrophils), OV (T cells CD8.), PRAD (T cells CD4 memory resting), READ (Macrophages M1), SARC (Macrophages M2), SKCM (Tregs), STAD (Tregs), TGCT (B cells naive), THCA (Dendritic cells activated), THYM (Macrophages M0), UCEC (T cells CD4 memory resting), UVM (Monocytes) and KIPR (T cells CD8) (Fig. 7 and S6 and Table S1). In addition, the expression level of CBLL1 was associated with various immune infiltrating cells in pan-cancer. For example, the expression level of CBLL1 was significantly correlated with immune cells such as BRCA B cells naive, B cells memory, T cells CD8, T cells CD4 memory activated, Tregs; HNSC B cells naive, B cells memory, T cells CD4 memory resting, NK cells activated; PRAD B cells naive, B cells memory, Plasma cells, T cells CD8, T cells CD4 memory resting (P < 0.05, Additional fle 1: Supplementary table S1).
The expression level of CBLL1 is related to immunomodulators, checkpoints and receptor molecules in pan-cancerous tumors
To further explore the relationship between CBLL1 mRNA expression and tumor immune markers, in order to understand the role of CBLL1 in pan-cancer immune escape. immunomodulators include immunostimulators, immunoinhibitors and MHC molecules. We found that the expression level of CBLL1 was associated with pan-cancer immunomodulators (Fig. 8A-C). For example, the expression level of CBLL1 was correlated with BLCA immunostimulators CD160, ADORA2A, TGFBR1, IL10RB and BTLA, with BRCA immunostimulators LGALS9, IL10RB, CD160, KDR, TGFBR1, etc., and with CESC immunostimulators KDR, ADORA2A, LAG3, LGALS9 and IL10RB (P < 0.05, Fig. 8A). The expression level of CBLL1 was correlated with BLCA immunoinhibitors TNFRSF4, TNFRSF14, CD276TNFRSF18, TNFSF9, TNFRSF25, BRCA immunoinhibitors TNFRSF4, TNFRSF14, ULBP1, MICB, TNFSF18, and CESC immunoinhibitors TNFSF9, TNFSF18, NT5ETNFRSF4, TNFSF13 (P < 0.05, Fig. 8B). The expression level of CBLL1 was significantly correlated with BLCA MHC molecules HLA-A, HLA-E, HLA-F, TAPBP and HLA-DPB1, BRCA MHC molecules HLA-A, HLA-F, HLA-EHLA-C, HLA-G, HLA-B, and CESC MHC molecules HLA-F, HLA-C, HLA-B, HLA-A, TAPBP (P < 0.05, Fig. 8C). In addition, the expression level of CBLL1 was associated with pancancerous immune checkpoint molecules (Fig. 8D). For example, the expression level of CBLL1 was correlated with BLCA checkpoint molecules CCL26, CCL14, CCL23, CCL21, CCL28; BRCA checkpoint molecules CCL26, CCL3, CCL17, CCL23, CX3CL1, CXCL2; CESC checkpoint molecules CXCL2, CXCL3, CCL3, CXCL16, CCL13 (P < 0.05, Fig. 8D). In addition, the expression level of CBLL1 was associated with receptor molecules (Fig. S7 and Table 4). For example, the expression level of CBLL1 is related to BLCA receptor molecules CCR9, CCR8, CCR4, CCR7 and CXCR5; BRCA receptor molecules CCR10, CCR8, CCR9, CCR4, CXCR3, etc; CESC molecules CCR8, XCR1, CCR2, CCR6, CCR4, etc (Table 4).