Dataset Information

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

SUBMITTER: Wang H

PROVIDER: S-EPMC8763391 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer.

Wang Hao H Yin Jinwen J Hong Yuntian Y Ren Anli A Wang Haizhou H Li Mengting M Zhao Qiu Q Jiang Congqing C Liu Lan L

Frontiers in cell and developmental biology 20220103

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucid ...[more]

PMID: 35047505

Similar Datasets

Project description:BackgroundThe kinesin-13 family member 2C (KIF2C) is a versatile protein participating in many biological processes. KIF2C is frequently up-regulated in multiple types of cancer and is associated with cancer development. However, the role of KIF2C in immune cell infiltration of tumor microenvironment and immunotherapy in breast cancer remains unclear.MethodsThe expression of KIF2C was analyzed using Tumor Immune Estimation Resource (TIMER) database and further verified by immunohistochemical staining in human breast cancer tissues. The correlation between KIF2C expression and clinical parameters, the impact of KIF2C on clinical prognosis and independent prognostic factors were analyzed by using TCGA database, the Kaplan-Meier plotter, and Univariate and multivariate Cox analyses, respectively. The nomograms were constructed according to independent prognostic factors and validated with C-index, calibration curves, ROC curves, and decision curve analysis. A gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms of KIF2C. The degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA (ssGSEA). The Tumor mutational burden and Tumor Immune Dysfunction and Rejection (TIDE) were used to analyze immunotherapeutic efficiency. Finally, the KIF2C-related competing endogenous RNA (ceRNA) network was constructed to predict the putative regulatory mechanisms of KIF2C.ResultsKIF2C was remarkably up-regulated in 18 different types of cancers, including breast cancer. Kaplan-Meier survival analysis showed that high KIF2C expression was associated with poor overall survival (OS). KIF2C expression was associated with clinical parameters such as age, TMN stage, T status, and molecular subtypes. We identified age, stage, estrogen receptor (ER) and KIF2C expression as OS-related independent prognosis factors for breast cancer. An OS-related nomogram was developed based on these independent prognosis factors and displayed good predicting ability for OS of breast cancer patients. Finally, our results revealed that KIF2C was significantly related to immune cell infiltration, tumor mutational burden, and immunotherapy in patients with breast cancer.ConclusionKIF2C was overexpressed in breast cancer and was positively correlated with immune cell infiltration and immunotherapy response. Therefore, KIF2C can serve as a potential biomarker for prognosis and immunotherapy in breast cancer.

Project description:Background: Sirtuin 7 (SIRT7), a protein-coding gene whose abnormal expression and function are associated with carcinogenesis. However, the prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear. Methods: The expression and survival data of SIRT7 in patients with breast cancer were analyzed using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interaction Analysis (GEPIA), The Human Protein Atlas (HPA), UALCAN, Breast Cancer Gene-Expression Miner (BC-GenExMiner), and Kaplan-Meier plotter databases. Also, the expression correlations between SIRT7 and immune infiltration gene markers were analyzed using TIMER and further verified the results using immunohistochemistry. Results: SIRT7 exhibited higher expression levels in breast cancer tissues than the adjacent normal tissues. SIRT7 expression was significantly correlated with sample type, subclass, cancer stage, menopause status, age, nodal status, estrogen receptor (ER), progesterone receptor (PR), and triple-negative status. High SIRT7 expression was associated with poor prognosis in breast cancer-luminal A [overall survival (OS): hazard ratio (HR) = 1.54, p = 1.70e-02; distant metastasis-free survival (DMFS): HR = 1.56, p = 2.60e-03]. Moreover, the expression of SIRT7 was positively correlated with the expression of IRF5 (M1 macrophages marker, r = 0.165, p = 1.13e-04) and PD1 (T cell exhaustion marker, r = 0.134, p = 1.74e-03). These results suggested that the expression of SIRT7 was related to M1 macrophages and T cell exhaustion infiltration in breast cancer-luminal. Conclusions: These findings demonstrate that the high expression of SIRT7 indicates poor prognosis in breast cancer as well as increased immune infiltration levels of M1 macrophages and T cell exhaustion in breast cancer-luminal. Thus, SIRT7 may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in breast cancer-luminal.

Project description:Background: ASB6, an E3 ubiquitin ligase, mediates the proteasomal degradation of its substrate proteins via the ubiquitin-proteasome pathway. ASB6 has been reported to play significant roles in several biological processes, including tumor stemness and endoplasmic reticulum stress. However, the underlying role and mechanism of ASB6 in colorectal cancer, particularly its association with immune infiltration levels and its prognostic significance, remain to be fully elucidated. Methods: We identified key prognostic genes in CRC patients through LASSO-penalized Cox regression, Univariate and Multivariate Cox regression analyses. Subsequently, we comprehensively analyzed the prognostic value of hub genes and constructed a prognostic nomogram. Finally, we identified ASB6 interacting proteins through immunoprecipitation-mass spectrometry (IP-MS) and constructed protein-protein interaction (PPI) networks and performed pathway enrichment analysis to explore the potential mechanisms of ASB6. Meanwhile, we evaluated the functions of ASB6 in CRC cells through in vitro cell experiments. Results: We identified ASB6 as a hub gene in CRC. ASB6 was highly expressed in CRC, and patients with high ASB6 expression had worse Disease-Free Interval (DFI), Disease-Specific Survival (DSS), Overall Survival (OS), and Progression-Free Interval (PFI). Correlation analysis showed that ASB6 expression were positively correlated with lymph node invasion and distal metastasis. Overexpression of ASB6 enhanced the migration ability of CRC cells. Multivariate Cox regression analysis revealed that ASB6 was an independent prognostic factor for OS and DSS in CRC. The nomogram model constructed based on multivariate analysis results had good predictive effects, with C-indexes of 0.811 and 0.934 for OS and DSS, respectively. Furthermore, analysis of immune infiltration levels showed that ASB6 expression were positively correlated with M2-type macrophage infiltration levels in CRC, and patients with high levels of both ASB6 and M2-type macrophages had a worse prognosis. Furthermore, pathway enrichment analysis of ASB6 interacting proteins identified by IP-MS suggested that ASB6 may play a crucial role through the response to unfolded protein pathway and protein processing in the endoplasmic reticulum pathway. Conclusions: ASB6 is significantly upregulated in CRC tissues and is a risk factor for prognosis in CRC patients. ASB6 enhances the migration ability of CRC cells. Therefore, ASB6 may be an independent prognostic biomarker and potential therapeutic target for CRC patients.

Project description:To characterize the implications of lipid metabolism-related gene thioesterase superfamily member 6 (THEM6) in breast cancer. Several databases including The Cancer Genome Atlas (TCGA) were utilized for our meticulous bioinformatics analysis. We further performed qRT-PCR, immunoblotting and IHC assays to validate the expression of THEM6 in various breast cancer cells and tissues. In addition, we have carried out relevant functional experiments to explore the regulatory role of THEM6 in vitro. Lipid metabolism-related genes are independent factors for overall survival. According to several databases, THEM6 was significantly more expressed in cancerous tissues of breast invasive carcinoma (BRCA) compared to its paracancerous tissues. Furthermore, THEM6 overexpression was correlated with poorer overall survival of BRCA patients, serving as a separate prognostic factor for BRCA. Biological functional analyses revealed that THEM6 was associated with tumor progression and pathogenesis. Finally, we discovered that in BRCA, THEM6 expression was linked to multiple immune cell types. qRT-PCR and Western blotting experiments demonstrated a general upregulation of THEM6 expression in breast carcinoma cells. IHC showed that THEM6 was expressed in both breast cancer tissues and para-cancer tissues, but its expression level was significantly higher in carcinoma tissues. In vitro studies indicated that THEM6 increased proliferation, invasion, and inhibited apoptosis of breast carcinoma cells, while also affecting the cell cycle and promoting cancer progression. Furthermore, THEM6 may influence macrophage recruitment and polarization in the tumor microenvironment by regulating CCL2 secretion, which in turn affects macrophage recruitment in the tumor microenvironment. Our findings indicate that the overexpression of THEM6, which is linked to the development of breast cancer, is a predictor of a poor prognosis and has an impact on the degree of immune cell infiltration. Therefore, THEM6 has the potential to be a valuable target for BRCA.

Dataset Information

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer.

Publications

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets