A novel signature based on immune‐related gene pairs and clinical features to predict prognosis and treatment effect in “driver gene negative” lung adenocarcinoma

Cai, He-Yuan; Yang, Hao-Shuai; Shan, Shi-Chao; Lei, Yiyan; Zou, Jianyong; Zhu, Ying; Hy, Luo

doi:10.1002/cam4.4577

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…[ 52 ] CMTM2 is one of immune-related genes and has a protective effect on some carcinomas. [ 18 ] Helicobacter pylori infection-related chronic inflammation is a leading cause of gastric cancer. [ 53 ] It has been reported that SJZ positively regulates innate immune response by increasing macrophages and is beneficial for gastrointestinal system.…”

Section: Discussionmentioning

confidence: 99%

“…CMTM2 is an immune-related gene belonging to CMTM2 family and closely related to tumor progression, recurrence, and prognosis in lung cancer, hepatocellular cancer, and GC. [17][18][19] However, the role of CMTM2 in GC progression is not fully elucidated. In the present study, we found that SJZ treatment elevated CMTM2 mRNA and protein expression levels, and suppressed the proliferation, migration, invasion, and cancer stem cell-like properties of GC cells.…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Effect of Si-Jun-Zi Decoction on SGC7901 Gastric Cancer Cells by CMTM2 Activation

Chen

Miao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The Si-Jun-Zi decoction (SJZ), a traditional Chinese medicine (TCM) formula, is used clinically against multiple malignancies, including gastric cancer (GC). In previous study, we have shown that SJZ plays an anticancer role in SGC7901 cell xenograft mice models. However, the underlying mechanisms are unclear. The objective of this study was to evaluate the effect and mechanism of SJZ on the proliferation, migration, invasion, and cancer stem cell-like properties of GC cells. High-throughput mRNA sequencing analysis was performed to investigate the global alterations in gene expression in xenograft tumors, and 56 significantly differentially expressed genes (43 upregulated and 13 downregulated genes) were identified between the SJZ group and the Model group totally. We focused on CMTM2, which was significantly increased after SJZ intervention, as a candidate target gene of SJZ. The results indicated that CMTM2 expression was elevated in SJZ-treated SGC7901 cells and knocking-down CMTM2 expression partially hampered the inhibitory effects of SJZ on the proliferation, migration, and invasion of GC cells. Moreover, SJZ treatment repressed the spheroid and colony-forming capacity in GC cells, accompanied by downregulation of stem cell markers including SOX2, NANOG, and CD44. CMTM2 knockdown antagonized the effects of SJZ on the cancer stem cell-like properties of SGC7901 cells. Thus, SJZ effectively suppressed the proliferation, migration, invasion, and cancer stem cell-like properties of GC cells in vitro by upregulating CMTM2 expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antitumor Effect of Si-Jun-Zi Decoction on SGC7901 Gastric Cancer Cells by CMTM2 Activation

Chen

Miao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“… 9 , 10 It was found that immune-related gene pairs (IRGPs) can be used as predictors of LUAD prognosis. 11 , 12 However, the exact IRGs-associated pathways and mechanisms of immune cells in LUAD and how these genes affect the prognosis of LUAD remain unclear, which is worth further exploration.…”

Section: Introductionmentioning

confidence: 99%

Construction and Validation of a Novel Immune-Related Gene Pairs-Based Prognostic Model in Lung Adenocarcinoma

Liu

Zhang

et al. 2023

Cancer Control

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Object Focus on immune-related gene pairs (IRGPs) and develop a prognostic model to predict the prognosis of patients with lung adenocarcinoma (LUAD). Methods First, the LUAD patient dataset was downloaded from The Cancer Genome Atlas database, and paired analysis of immune-related genes was subsequently conducted. Then, LASSO regression was used to screen prognostic IRGPs for building a risk prediction model. Meanwhile, the Gene Expression Omnibus database was used for external validation of the model. Next, the clinical predictive power of IRGPs features was assessed by uni-multivariate Cox regression analysis, the infiltration of key immune cells in high and low IRGPs risk groups was analyzed with CIBERSORT, quanTIseq, and Timer, and the key pathways enriched for IRGPs were assessed using the Kyoto Encyclopedia of Genes and Genomes. Finally, the expression and related functions of key immune cells and genes were verified by immunofluorescence and cell experiments of tissue samples. Results It was revealed that the risk score of 19 IRGPs could be used as accurate indicators to evaluate the prognosis of LUAD patients, and the risk score was mainly related to T cell infiltration based on CIBERSORT analysis. Two genes of IRGPs, IL6, and CCL2, were found to be closely associated with the expression of PD-1/PD-L1 and the function of T-cells. Depending on the results of tissue immunofluorescence, IL6, CCL2, and T cells were highly expressed in the LUAD tissues of patients. Furthermore, IL6 and CCL2 were positively correlated with the expression of T cells. Besides, qRT-PCR assay in four different LUAD cells proved that IL6 and CCL2 were positively correlated with the expression of PD-L1 (P < .001). Conclusions Based on 19 IRGPs, an effective prognosis model was established to predict the prognosis of LUAD patients. In addition, IL6 and CCL2 are closely related to the function of T-cells.

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A novel signature based on immune‐related gene pairs and clinical features to predict prognosis and treatment effect in “driver gene negative” lung adenocarcinoma

et al. 2022

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Objective Examining the role of immune‐related genes (IRGs) in “driver gene negative” lung adenocarcinoma (LUAD) may provide new ideas for the treatment and study for this LUAD subgroup. We aimed to find the hub immune‐related gene pairs can stratify the risk of “driver‐gene‐negative” LUAD. Materials and Methods IRGs were identified according to ImmPort database based on RNA sequencing results of tumors and normal tissues from 46 patients with “driver gene negative” LUAD at The First Affiliated Hospital of Sun Yat‐sen University and cyclically singly paired as immune‐related gene pairs (IRGPs). Multivariate Cox analysis was used to construct an immune risk model and a prognostic nomogram combining was also been developed. Immune microenvironment landscape described by CIBERSORT and drug sensitivity calculated by pRRophetic algorithm were used to explore possible treatment improvements. Results A novel immune risk model with 5‐IRGPs (CD1A|CXCL135, CD1A|S100A7L2, IFNA7|CMTM2, IFNA7|CSF3, CAMP|TFR2) can accurately distinguish patients in the high‐ and low‐risk groups. Risk score act as an independent prognostic factor and is related to clinical stage. There are significant differences in tumor immune microenvironment and PD‐1/PD‐L1/CTLA‐4 expression between groups. The low‐risk patient may benefit more from the commonly used chemotherapy regimens such as gemcitabine and paclitaxel. Conclusion This study constructed 5‐IRGPs as a reliable prognostic tool and may represent genes pairs that are potential rationale for choice of treatment for “driver gene negative” LUAD.

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A novel signature based on immune‐related gene pairs and clinical features to predict prognosis and treatment effect in “driver gene negative” lung adenocarcinoma

Cited by 4 publications

References 42 publications

Antitumor Effect of Si-Jun-Zi Decoction on SGC7901 Gastric Cancer Cells by CMTM2 Activation

Antitumor Effect of Si-Jun-Zi Decoction on SGC7901 Gastric Cancer Cells by CMTM2 Activation

Construction and Validation of a Novel Immune-Related Gene Pairs-Based Prognostic Model in Lung Adenocarcinoma

A novel signature based on immune‐related gene pairs and clinical features to predict prognosis and treatment effect in “driver gene negative” lung adenocarcinoma

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