Identification of pyroptosis-related subtypes, development of a prognostic model, and characterization of tumour microenvironment infiltration in gastric cancer

Cao, Feng; Hu, Jingtao; Yuan, Huatang; Cao, Pengwei; Cheng, Yunsheng; Wang, Yong

doi:10.3389/fgene.2022.963565

Cited by 4 publications

(1 citation statement)

References 73 publications

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“…In our study, we developed a PRS based on a comprehensive analysis of pyroptosis. Previous studies of pyroptosis in GC have elucidated the crucial role of pyroptosis in the TME through bioinformatics analysis, providing insights into predicting the prognosis of patients with GC and their response to immunotherapy 22 - 24 . The strength of our study lies in the validation of the findings from public databases using transcriptomic and exomic data from our center.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer

Wang,

Gao,

et al. 2024

Theranostics

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Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRS low is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRS low marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.

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Section: Discussionmentioning

confidence: 99%

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer

Wang,

Gao,

et al. 2024

Theranostics

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Eupafolin hinders cross-talk between gastric cancer cells and cancer-associated fibroblasts by abrogating the IL18/IL18RAP signaling axis

Yan,

Wang,

Zhou

et al. 2024

Phytomedicine

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Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer

Liu,

Zhou,

Liu

et al. 2024

Cell Death Dis

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Colorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.

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Identification of pyroptosis-related subtypes, development of a prognostic model, and characterization of tumour microenvironment infiltration in gastric cancer

Cited by 4 publications

References 73 publications

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer

Eupafolin hinders cross-talk between gastric cancer cells and cancer-associated fibroblasts by abrogating the IL18/IL18RAP signaling axis

Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer

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