TIMP2 is associated with prognosis and immune infiltrates of gastric and colon cancer.

Tissue inhibitor of metalloproteinase-2 (TIMP2), a member of tissue inhibitors of the metalloproteinase (TIMP) family is associated with the progression of various tumors. However, the association of TIMP2 with cancer prognosis and tumor-infiltrating lymphocytes remains unclear. TIMP2 expression was analyzed by Tumor Immune Estimation Resource (TIMER), TNM plot, Gene Expression Profiling Interactive Analysis (GEPIA) database, and 50 paired gastric cancer tissues. We evaluated the influence of TIMP2 on clinical prognosis using the Kaplan-Meier plotter, the PrognoScan database, GEPIA, and TCGA data. The correlation of TIMP2 with tumor immune infiltrates and the set of gene markers of immune infiltrates was investigated by TIMER and GEPIA. TIMP2 is highly expressed in gastric cancer and slightly expressed in colon cancer. High TIMP2 expression was significantly correlated with poor overall survival (OS, hazard ratio [HR] = 1.38, 95% confidence interval [CI]: [1.16-1.63]; P = 0.0002) and progression-free survival (PFS, HR = 1.39, 95% CI: [1.14-1.7]; P = 0.0012) in gastric cancers. Specifically, high TIMP2 expression was associated with poorer OS and PFS, but not with OS and PFS in stage 1 (OS HR = 1.96, P = 0.29; PFS HR = 0.43, P = 0.19) and stage 2 (OS HR = 1.59, P = 0.12; PFS HR = 1.47, P = 0.2) and stage N0 patients (OS HR = 1.6, P = 0.35; PFS HR = 1.56, P = 0.38) of gastric cancer patients. There was a significant positive correlation between TIMP2 expression and different types of immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in the stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD). Moreover, TIMP2 expression was strongly correlated with different sets of immune markers. These results suggest that TIMP2 is associated with prognosis and level of immune infiltration in a variety of cancers, especially colon and gastric cancer patients. Moreover, the expression of TIMP2 potentially contributes to the regulation of tumor-associated macrophages (TAMs), dendritic cells, T cell exhaustion, and Tregs in colon and gastric cancer. These findings suggest that TIMP2 may serve as a prognostic biomarker for predicting prognosis and immune infiltration in gastric and colon cancer.

Jian F ，Yanhong J ，Limeng W ，Guoping N ，Yiqing T ，Hao L ，Zhaoji P ... -  《-》

LAYN Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric and Colon Cancers.

Pan JH ，Zhou H ，Cooper L ，Huang JL ，Zhu SB ，Zhao XX ，Ding H ，Pan YL ，Rong L ... -  《Frontiers in Immunology》

CMA1 is potent prognostic marker and associates with immune infiltration in gastric cancer.

Shi S ，Ye S ，Mao J ，Ru Y ，Lu Y ，Wu X ，Xu M ，Zhu T ，Wang Y ，Chen Y ，Tang X ，Xi Y ... -  《-》

RAI14 Is a Prognostic Biomarker and Correlated With Immune Cell Infiltrates in Gastric Cancer.

Xiao Y ，Zhang H ，Du G ，Meng X ，Wu T ，Zhou Q ，Wang Y ，Tan B ... -  《-》

Six Cell Cycle-related Genes Serve as Potential Prognostic Biomarkers and Correlated with Immune Infiltrates in Hepatocellular Carcinoma.

Background: Cell cycle-related genes (CDK1, CDK5, CDC20, CCNA2, CCNB1, and CCNB2) play important roles in the regulation of mitotic cell cycle in eukaryotes. However, the correlation between cell cycle-related genes and tumor-infiltrating and prognosis of hepatocellular carcinoma (HCC) needs further investigation. Methods: Two public websites, Tumor Immune Estimate Resource (TIMER) and Oncomine, were used to assess the expression levels of cycle-related genes. We also analyzed the protein expression levels of six cell cycle-related genes using the HPA database. In addition, Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) database were used to investigate the impact of cell cycle-related gene expression levels on the clinical prognosis of HCC. The correlation between cell cycle-related genes and cancer immune infiltrates was analyzed through TIMER site. Subsequently, GEPIA and TIMER database were used to assess the correlation between the expression of six cell cycle-related genes and polygenic markers in monocytes and macrophages, respectively. The cell cycle-related genes were also analyzed to find the associated genes with the highest alteration frequency, by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) approaches of Metascape and String database, respectively. Results: The expression levels of cell cycle-related genes were up-regulated in tumor tissues compared with normal tissues. Subsequently, the expression of high cell cycle-related genes was positively correlated with poor overall survival (OS) and progression-free survival (PFS) in HCC, for CDK1 (OS: HR = 2.15, P = 1.1E-05 PFS: HR = 2.03, P = 2.3E-06), CDK5 (OS: HR = 1.85, P = 0.0035 PFS: HR = 1.26, P = 0.17), CDC20 (OS: HR = 2.49, P = 5.1E-07 PFS: HR = 1.77, P = 0.00012), CCNA2 (OS: HR = 1.92, P = 0.00018 PFS: HR = 1.96, P = 5.2E-06), CCNB1 (OS: HR = 2.34, P = 3.4E-05 PFS: HR = 1.97, P = 5.3E-06), and CCNB2 (OS: HR = 1.91, P = 0.0013 PFS: HR = 1.63, P = 0.0011), respectively. Furthermore, the transcription level of cell cycle-related genes was significantly correlated with immune infiltrating levels of CD4+ T and CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs) in HCC, respectively. Amongst them, the expression levels of CDK1, CDC20, CCNA2, CCNB1 and CCNB2 manifest strongly correlated with diverse immune marker sets in HCC. Conclusions: Our results demonstrated that cell cycle-related genes played key roles in the prognosis of HCC. Meanwhile, they were significantly correlated with immune infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, macrophages and DCs in HCC, respectively. In addition, CDK1, CDC20, CCNA2, CCNB1 and CCNB2 expressions may be involved in the regulation of monocytes and tumor-associated macrophages (TAMs) in HCC, respectively. These findings strongly suggested that cell cycle-related genes could be used as novel biomarkers for exploring the prognosis and immune cells infiltration of HCC.

Shi Y ，Sang X ，Deng J ，Wang Y ，Chen X ，Lin S ，Wu F ，Xu A ... -  《-》