LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response

Huang, Jihong; Liang, Yuan; Huang, Wenqi; Liao, Lili; Zhu, Xi; Wang, Xiaoqing; Li, Jiaxin; Liang, Wenyu; Wu, Yuting; Liu, Xiaocheng; Yu, Dong; Zheng, Yunna; Guan, Jian; Zhan, Yiqiang; Liu, Laiyu

doi:10.3389/fimmu.2022.1064874

Cited by 3 publications

(1 citation statement)

References 50 publications

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“… 30 KRT6A was a gene that mediates tumor-associated macrophage activity and tumors with high KRT6A have a hot immunophenotype with increased abundance of immune cells and increased activity of immune-related pathways. 31 How they work in A20-mediated immune evasion need further study. In addition, the STC1 mRNA levels were also increased by A20 overexpression.…”

Section: Discussionmentioning

confidence: 99%

A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block “eat-me” signal

Luo,

Wang,

et al. 2023

Sig Transduct Target Ther

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Immune checkpoint inhibitors (ICIs) have induced durable clinical responses in a subset of patients with colorectal cancer (CRC). However, the dis-satisfactory response rate and the lack of appropriate biomarkers for selecting suitable patients to be treated with ICIs pose a major challenge to current immunotherapies. Inflammation-related molecule A20 is closely related to cancer immune response, but the effect of A20 on “eat-me” signal and immunotherapy efficacy remains elusive. We found that A20 downregulation prominently improved the antitumor immune response and the efficacy of PD-1 inhibitor in CRC in vitro and in vivo. Higher A20 expression was associated with less infiltration of immune cells including CD3 (+), CD8 (+) T cells and macrophages in CRC tissues and also poorer prognosis. Gain- and loss-A20 functional studies proved that A20 could decrease the “eat-me” signal calreticulin (CRT) protein on cell membrane translocation via upregulating stanniocalcin 1 (STC1), binding to CRT and detaining in mitochondria. Mechanistically, A20 inhibited GSK3β phosphorylating STC1 at Thr86 to slow down the degradation of STC1 protein. Our findings reveal a new crosstalk between inflammatory molecule A20 and “eat-me” signal in CRC, which may represent a novel predictive biomarker for selecting CRC patients most likely to benefit from ICI therapy.

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Section: Discussionmentioning

confidence: 99%

A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block “eat-me” signal

Luo,

Wang,

et al. 2023

Sig Transduct Target Ther

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Integrated single-cell and bulk RNA-Seq analysis enhances prognostic accuracy of PD-1/PD-L1 immunotherapy response in lung adenocarcinoma through necroptotic anoikis gene signatures

Sui,

Liu,

Zhong

et al. 2024

Sci Rep

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In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model’s utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model.

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Implications of different cell death patterns for prognosis and immunity in lung adenocarcinoma

Zhou,

Gao,

et al. 2023

npj Precis. Onc.

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In recent years, lung adenocarcinoma (LUAD) has become a focus of attention due to its low response to treatment, poor prognosis, and lack of reliable indicators to predict the progression or therapeutic effect of LUAD. Different cell death patterns play a crucial role in tumor development and are promising for predicting LUAD prognosis. From the TCGA and GEO databases, we obtained bulk transcriptomes, single-cell transcriptomes, and clinical information. Genes in 15 types of cell death were analyzed for cell death index (CDI) signature establishment. The CDI signature using necroptosis + immunologic cell death-related genes was established in the TCGA cohort with the 1-, 2-, 3-, 4- and 5-year AUC values were 0.772, 0.736, 0.723, 0.795, and 0.743, respectively. The prognosis was significantly better in the low CDI group than in the high CDI group. We also investigated the relationship between the CDI signature and clinical variables, published prognosis biomarkers, immune cell infiltration, functional enrichment pathways, and immunity biomarkers. In vitro assay showed that HNRNPF and FGF2 promoted lung cancer cell proliferation and migration and were also involved in cell death. Therefore, as a robust prognosis biomarker, CDI signatures can screen for patients who might benefit from immunotherapy and improve diagnostic accuracy and LUAD patient outcomes.

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LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response

Cited by 3 publications

References 50 publications

A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block “eat-me” signal

A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block “eat-me” signal

Integrated single-cell and bulk RNA-Seq analysis enhances prognostic accuracy of PD-1/PD-L1 immunotherapy response in lung adenocarcinoma through necroptotic anoikis gene signatures

Implications of different cell death patterns for prognosis and immunity in lung adenocarcinoma

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