Prognostic value and immunological role of Kruppel-like transcription factor 9 gene in pan-carcinoma

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  Figure 1.. Pan-carcinoma analysis on the expression levels of KLF9 mRNA. The expression of KLF9 was reduced relative to paracancerous tissues in multiple tumors, such as BLCA, BRCA, CESC, CHOL, COAD, ESCA, HNSC, KICH, KIRC, KIRP, LIHC, LUAD, LUSC, PRAD, READ, STAD, THCA, and UCEC. Red fusiformis represents tumor tissue and blue fusiformis represents normal tissue. ACC = adrenocortial carcinoma, BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, CESC = cervical squamous cell carcinoma and endovervical adenocarcinoma, CHOL = cholangiocarcinoma, COAD = colon adenocarcinoma, DLBC = lymphoid neoplasm diffuse large B-cell lymphoma, ESCA = esophageal carcinoma, GBM = glioblastoma multiforme, GSEA = the gene set enrichment analysis, HNSC = head and neck squamous cell carcinoma, KICH = kidney chromophobe, KIRC = kidney renal clear cell carcinoma, KIRP = kidney renal papillary cell carcinoma, KLF9 = Kruppel-like transcription factor 9, LAML = acute myeloid leukemia, LGG = brain lower grade glioma, LIHC = liver hepatocellular carcinoma, LUAD = lung adenocarcinoma, LUSC = lung squamous cell carcinoma, MESO = mesothelioma, OV = ovarian serous cystadenocarcinoma, PAAD = pancreatic…

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  Figure 2.. Comparison of Kaplan–Meier survival curves between high and low expressions of KLF9 gene in different types of tumors. We analyzed the relationship between KLF9 expression and overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). KLF9 can act as a protective factor to improve the prognosis of carcinoma patients in some tumor types, especially in KIRC, MESO, and SKCM. KIRC (OS, P value < .001), LAML (OS, P value = .042), MESO (OS, P value = .015), STAD (OS, P value = .020), SKCM (OS, P value < .001), KIRC (DSS, P value < .001), MESO (DSS, P value = .033), SKCM (DSS, P value < .001), KIRC (PFI, P value < .001), MESO (PFI, P value = .011), SKCM (PFI, P value = .004), UCS (PFI, P value = .049). Notably, no significant association was found between KLF9 expression and DFI across all tumor types. KIRC = kidney renal clear cell carcinoma, KLF9 = Kruppel-like transcription factor 9, LAML = acute myeloid leukemia, MESO = mesothelioma, SKCM = skin cutaneous meianoma, STAD = Stomach adenocarcinoma, UCS = uterine carcinosarcoma.

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  Figure 3.. Correlation analysis was used to analyze the correlation between the expression and survival of KLF9 mRNA in different types of TCGA tumors. Univariate Cox proportional hazards regression model was used to analyze the relationship between KLF9 expression and OS (A), DDS (B), DFI (C) and DPI (D) in various carcinomas, so as to observe the relationship between KLF9 expression and tumor prognosis. ACC = adrenocortial carcinoma, BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, CESC = cervical squamous cell carcinoma and endovervical adenocarcinoma, CHOL = cholangiocarcinoma, COAD = colon adenocarcinoma, DFI = disease-free interval, DLBC = lymphoid neoplasm diffuse large B-cell lymphoma, DSS = disease-specific survival, ESCA = esophageal carcinoma, HNSC = head and neck squamous cell carcinoma, KICH = kidney chromophobe, KIRC = kidney renal clear cell carcinoma, KIRP = kidney renal papillary cell carcinoma, KLF9 = Kruppel-like transcription factor 9, LGG = brain lower grade glioma, LIHC = liver hepatocellular carcinoma, LUAD = lung adenocarcinoma, LUSC = lung squamous cell carcinoma, MESO = mesothelioma, OS = overall survival, OV = ovarian serous…

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  Figure 4.. Correlation between KLF9 expression and clinicopathology of pan-carcinoma. KLF9 was closely related to the clinical stages of various carcinomas. KLF9 was highly expressed in stage III patients but less expressed in stage II patients affected by BLCA, BRCA, ESCA, and LUSC. However, the expression of KLF9 in TGCT showed the opposite result. In KIRC, KLF9 was highly expressed in stage I patients but less expressed in stage IV patients. In other tumor types, no association was found between KLF9 expression and clinicopathological features. ACC = adrenocortial carcinoma, BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, CHOL = cholangiocarcinoma, COAD = colon adenocarcinoma, ESCA = esophageal carcinoma, HNSC = head and neck squamous cell carcinoma, KICH = kidney chromophobe, KIRC = kidney renal clear cell carcinoma, KIRP = kidney renal papillary cell carcinoma, KLF9 = Kruppel-like transcription factor 9, LIHC = liver hepatocellular carcinoma, LUAD = lung adenocarcinoma, LUSC = lung squamous cell carcinoma, MESO = mesothelioma, PAAD = pancreatic adenocarcinoma, READ = rectum adenocarcinoma, SKCM = skin cutaneous meianoma, STAD = stomach adenocarcinoma, TGCT =…

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  Figure 5.. Association of KLF9 expression with TMB and MSI in pan-carcinoma. (A) The expression of KLF9 was associated with TMB in some tumor types (n = 13). Thereinto, the expression of KLF9 was positively correlated with TMB only in COAD and THYM, but negatively correlated with other tumor types, including BLCA, THCA, TGCT, STAD, PRAD, PAAD, LUSC, LUAD, LGG, KIRC and ERCA. (B) The expression of KLF9 was associated with MSI in some tumor types (n = 11). Thereinto, the expression of KLF9 was positively correlated with MSI only in COAD and READ, but negatively correlated with other tumor types, including CESC, Lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), HNSC, KIRP, LUAD, PRAD, STAD, TGCT and UCS. ACC = adrenocortial carcinoma, BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, CESC = cervical squamous cell carcinoma and endovervical adenocarcinoma, CHOL = cholangiocarcinoma, COAD = colon adenocarcinoma, ESCA = esophageal carcinoma, GBM = glioblastoma multiforme, HNSC = head and neck squamous cell carcinoma, KICH = kidney chromophobe, KIRC = kidney renal clear cell carcinoma, KIRP = kidney renal papillary cell carcinoma, KLF9 = Kruppel-like transcription factor…

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  Figure 6.. Correlation between KLF9 expression and TME in pan-carcinoma. (A) KLF9 was positively correlated with the immune cell in multiple tumors. BLCA: R = 0.49, P value < 2.2e-16, BRCA: R = 0.13, P value = 1.2e-05, COAD, R = 0.34, P value = 4.6e-14, ESCA: R = 0.7, P value = 1.6e-6, LUAD: R = 0.16, P value = 0.00029, LUSC: R = 0.36, P value < 2.2e-16, OV: R = 0.31, P value = 6.8e-10, PAAD: R = 0.41, P value = 2.3e-08, PRAD: R = 0.15, P value = 8e-04, STAD: R = 027, P value = 87e-08. (B) The expression of KLF9 was positively correlated with the expression of stromal cells. BLCA: R = 0.7, P value < 2.2e-16, BRCA: R = 0.44, P value = 2.2e-16, COAD, R = 0.46, P value < 2.2e-16, ESCA: R = 0.54, P value < 2.2e-16, LUAD: R = 0.33, P value = 1.7e-14, LUSC: R = 0.48, P value < 2.2e-16, OV: R = 0.34, P value = 1.1e-11, PAAD: R = 0.53, P value < 2.2e-16, PRAD: R = 0.33, P value = 5.8e-14, STAD: R = 061, P value < 2.2e-16. BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, COAD = colon adenocarcinoma, ESCA = esophageal carcinoma, KLF9 = Kruppel-like transcription factor 9, LUAD = lung adenocarcinoma, LUSC = lung squamous cell carcinoma, OV = ovarian serous cystadenocarcinoma,…

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  Figure 7.. Relationship between KLF9 expression and immune cell infiltration in Pan-carcinoma. (A) The expression of KLF9 was negatively correlated with B cell memory in multiple tumors, including BLCA (R = −0.22, P value < 4.3e-05), BRCA (R = −0.15, P value < 6e-07), CESC (R = −0.21, P value = .00037), COAD (R = −0.17, P value = .00045), KIRC (R = −0.18, P value < 2.4e-05), PAAD (R = −0.34, P value = 4.4e-06) and PRAD (R = −0.22, P value < 3.5e-05). (B) The expression of KLF9 was negatively correlated with dendritic cells activated in BLCA (R = −0.2, P value = .00015) and ESCA (R = −0.28, P value = .00062), and the same was true for T cells CD4 naïve in THYM (R = −0.31, P value = .00065) (C). (D) B cell naive was positively correlated with KLF9 expression in BLCA (R = 0.23, P value = 2.2e-05), BRCA (R = −0.25, P value < 2.2e-16), CESC (R = −0.27, P value < 2.5e-06), ESCA (R = −0.32, P value = 7.3e-05), HNSC (R = −0.26, P value = 4.1e-06), KIRC (R = −0.17, P value = .00012), MESO (R = −0.36, P value = 0.00083), PRAD (R = −0.19, P value = .00035), STAD (R = −0.19, P value = 3e-04) and TGCT (R = −0.4, P value = 3.7e-07). (E) T cells CD4 memory resting was also positively correlated with KLF9…

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  Figure 8.. Co-expression analysis of immune gene and KLF9 gene. The correlation between KLF9 expression and immune cells varied with different tumor types. The horizontal axis represents the type of carcinoma, the vertical axis represents the immune gene, and each small rectangular module represents the co-expression of immune gene and KLF9 gene in carcinomas. ACC = adrenocortial carcinoma, BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, CESC = cervical squamous cell carcinoma and endovervical adenocarcinoma, CHOL = cholangiocarcinoma, COAD = colon adenocarcinoma, DLBC = lymphoid neoplasm diffuse large B-cell lymphoma, ESCA = esophageal carcinoma, GBM = glioblastoma multiforme, HNSC = head and neck squamous cell carcinoma, KICH = kidney chromophobe, KIRC = kidney renal clear cell carcinoma, KIRP = kidney renal papillary cell carcinoma, KLF9 = Kruppel-like transcription factor 9, LAML = acute myeloid leukemia, LGG = brain lower grade glioma, LIHC = liver hepatocellular carcinoma, LUAD = lung adenocarcinoma, LUSC = lung squamous cell carcinoma, MESO = mesothelioma, OV = ovarian serous cystadenocarcinoma, PAAD = pancreatic adenocarcinoma, PCPG = pheochromocytoma and…

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  Figure 9.. Analysis of KLF9 pathway in different tumors. The KEGG pathway of KLF9 was analyzed in different types of carcinoma. Different color curves indicate the regulatory role of KLF9 gene on different functions or pathways in different carcinomas. Upward curve peaks indicate positive regulation, and downward curve peaks indicate negative regulation. ACC = adrenocortial carcinoma, BLCA = bladder urothelial carcinoma, BRCA = breast invasive carcinoma, CESC = cervical squamous cell carcinoma and endovervical adenocarcinoma, CHOL = cholangiocarcinoma, HNSC = head and neck squamous cell carcinoma, KEGG = Kyoto Encyclopedia of Genes and Genomes, KIRC = kidney renal clear cell carcinoma, KLF9 = Kruppel-like transcription factor 9, LAML = acute myeloid leukemia, LIHC = liver hepatocellular carcinoma, LUSC = lung squamous cell carcinoma, OV = ovarian serous cystadenocarcinoma, PCPG = pheochromocytoma and paraganglioma, READ = rectum adenocarcinoma, SARC = sarcoma, STAD = Stomach adenocarcinoma, TGCT = teaticular germ cell tumors.