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Updated: May 6, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
PANoptosis subtypes predict prognosis and immune efficacy in gastric cancer
Zitao Liu1, Liang Sun1, Xingyu Peng1
1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1 MinDe Road, Nanchang, 330006, Jiangxi, People's Republic of China.
Abstract:
PANoptosis is a form of inflammatory programmed cell death that is regulated by the PANoptosome. This PANoptosis possesses key characteristics of pyroptosis, apoptosis, and necroptosis, yet cannot be fully explained by any of these cell death modes. The unique nature of this cell death mechanism has garnered significant interest. However, the specific role of PANoptosis-associated features in gastric cancer (GC) is still uncertain. Patients were categorized into different PAN subtypes based on the expression of genes related to the PANoptosome. We conducted a systematic analysis to investigate the variations in prognosis and tumor microenvironment (TME) among these subtypes. Furthermore, we developed a risk score, called PANoptosis-related risk score (PANS), which is constructed from genes associated with the PANoptosis. We comprehensively analyzed the correlation between PANS and GC prognosis, TME, immunotherapy efficacy and chemotherapeutic drug sensitivity. Additionally, we performed in vitro experiments to validate the impact of Keratin 7 (KRT7) on GC. We identified two PAN subtypes (PANcluster A and B). PANoptosome genes were highly expressed in PANcluster A. PANcluster A has the characteristics of favorable prognosis, abundant infiltration of anti-tumor lymphocytes, and sensitivity to immunotherapy, thus it was categorized as an immune-inflammatory type. Meanwhile, our constructed PANS can effectively predict the prognosis and immune efficacy of GC. Patients with low PANS have a good prognosis, and have the characteristics of high tumor mutation load (TMB), high microsatellite instability (MSI), low tumor purity and sensitivity to immunotherapy. In addition, PANS can also identify suitable populations for different chemotherapy drugs. Finally, we confirmed that KRT7 is highly expressed in GC. Knocking down the expression of KRT7 significantly weakens the proliferation and migration abilities of GC cells. The models based on PANoptosis signature help to identify the TME features of GC and can effectively predict the prognosis and immune efficacy of GC. Furthermore, the experimental verification results of KRT7 provide theoretical support for anti-tumor treatment.
Insights
PANoptosis, an inflammatory cell death, is linked to gastric cancer prognosis. A new PANoptosis-related risk score (PANS) predicts patient outcomes, immune response, and chemotherapy sensitivity, with KRT7 validated as a therapeutic target.
Area of Science:
- Cell Death Research
- Cancer Biology
- Immunology
Background:
- PANoptosis is a distinct inflammatory programmed cell death pathway regulated by the PANoptosome, sharing features with pyroptosis, apoptosis, and necroptosis.
- The precise role of PANoptosis and its associated molecular mechanisms in gastric cancer (GC) remains largely uncharacterized.
- Understanding PANoptosis in GC is crucial for developing novel diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the prognostic and tumor microenvironment (TME) variations among different PANoptosis subtypes in gastric cancer.
- To develop and validate a PANoptosis-related risk score (PANS) for predicting GC prognosis, immune efficacy, and chemotherapeutic drug sensitivity.
- To experimentally validate the role of Keratin 7 (KRT7) in gastric cancer progression.
Main Methods:
- Patients were classified into PANoptosis subtypes based on PANoptosome gene expression.
- Systematic analysis of prognosis and TME features across subtypes.
- Development and validation of a PANoptosis-related risk score (PANS).
- Correlation analysis of PANS with GC prognosis, TME, immunotherapy, and chemotherapy sensitivity.
- In vitro experiments to assess the functional role of KRT7 in GC cells.
Main Results:
- Two PAN subtypes (PANcluster A and B) were identified, with PANcluster A exhibiting high PANoptosome gene expression, favorable prognosis, anti-tumor immune cell infiltration, and immunotherapy sensitivity.
- The developed PANS effectively predicted GC prognosis and immune efficacy. Low PANS scores correlated with good prognosis, high tumor mutation burden (TMB), high microsatellite instability (MSI), low tumor purity, and immunotherapy sensitivity.
- KRT7 was found to be highly expressed in GC, and its knockdown significantly inhibited GC cell proliferation and migration.
Conclusions:
- PANoptosis signatures can effectively characterize TME features in gastric cancer and predict patient prognosis and immunotherapy response.
- The PANS serves as a valuable tool for predicting clinical outcomes and guiding therapeutic strategies, including immunotherapy and chemotherapy selection.
- KRT7 represents a potential therapeutic target for gastric cancer, with its inhibition showing anti-tumor effects.
