Low baseline cGAS expression is associated with longer progression-free survival in patients with pleural mesothelioma
DOKPE
- Torchiat, Antoine ORCID University of Fribourg
- Silina, Karina ORCID Univerisy of Zurich
- Nair, Arya Ashok ORCID University of Fribourg
- Heeb, Laura Viktoria ORCID University of Fribourg
- Opitz, Isabelle ORCID University Hospital Zurich
- Gupta, Anurag ORCID University of Fribourg
- Curioni-Fontecedro, Alessandra ORCID HFR Fribourg Hôpital cantonal
- 2026
Published in:
- Lung Cancer. - Elsevier BV. - 2026, vol. 219, p. 109553
English
Introduction: The cyclic GMP-AMP synthase (cGAS)/STING pathway, a central DNA-sensing mechanism, is known
to activate anti-tumor immune response but may also promote tumor progression when chronically activated.
Given the role of asbestos-induced chronic inflammation in pleural mesothelioma (PM), we investigated cGAS/
STING expression and its association with treatment outcomes.
Methods: We analyzed tissue microarrays from 190 PM patients using multiparameter immunofluorescence
single-cell imaging. cGAS and STING expression were quantified in Calretinin+tumor cells, Calretinin-CD8-DC-
LAMP- cells, and CD8+cells before and after chemotherapy. Associations with treatment response and survival
were assessed.
Results: In matched pre- and post-treatment samples, total cGAS+cell frequency increased after chemotherapy, as
did cGAS+ frequencies in Calretinin+ tumor cells, Calretinin-CD8-DC-LAMP- cells, and CD8+cells after FDR
correction, whereas STING+cell frequency did not differ. Within the progressive-disease subgroup, significant
paired increases were retained for total cGAS+cells and Calretinin-CD8-DC-LAMP- cells. However, the magnitude
of change did not differ significantly among patients with partial response, stable disease, or progressive disease.
Low baseline total cGAS+ frequency and cGAS+ frequency in Calretinin-CD8-DC-LAMP- cells were associated
with longer progression-free survival. In an exploratory analysis of the TCGA PM cohort, higher CGAS/MB21D1
transcript expression was associated with shorter overall survival in continuous Cox regression, whereas STING1
transcript expression was not significantly associated with overall survival when analyzed as a continuous
variable.
Conclusions: Low baseline cGAS+ frequency, particularly in the Calretinin-CD8-DC-LAMP- compartment, was
associated with longer progression-free survival in PM. These findings support further evaluation of cGAS as a
candidate prognostic biomarker but do not establish cGAS as a predictor of chemotherapy response or as a causal
driver of treatment resistance.
to activate anti-tumor immune response but may also promote tumor progression when chronically activated.
Given the role of asbestos-induced chronic inflammation in pleural mesothelioma (PM), we investigated cGAS/
STING expression and its association with treatment outcomes.
Methods: We analyzed tissue microarrays from 190 PM patients using multiparameter immunofluorescence
single-cell imaging. cGAS and STING expression were quantified in Calretinin+tumor cells, Calretinin-CD8-DC-
LAMP- cells, and CD8+cells before and after chemotherapy. Associations with treatment response and survival
were assessed.
Results: In matched pre- and post-treatment samples, total cGAS+cell frequency increased after chemotherapy, as
did cGAS+ frequencies in Calretinin+ tumor cells, Calretinin-CD8-DC-LAMP- cells, and CD8+cells after FDR
correction, whereas STING+cell frequency did not differ. Within the progressive-disease subgroup, significant
paired increases were retained for total cGAS+cells and Calretinin-CD8-DC-LAMP- cells. However, the magnitude
of change did not differ significantly among patients with partial response, stable disease, or progressive disease.
Low baseline total cGAS+ frequency and cGAS+ frequency in Calretinin-CD8-DC-LAMP- cells were associated
with longer progression-free survival. In an exploratory analysis of the TCGA PM cohort, higher CGAS/MB21D1
transcript expression was associated with shorter overall survival in continuous Cox regression, whereas STING1
transcript expression was not significantly associated with overall survival when analyzed as a continuous
variable.
Conclusions: Low baseline cGAS+ frequency, particularly in the Calretinin-CD8-DC-LAMP- compartment, was
associated with longer progression-free survival in PM. These findings support further evaluation of cGAS as a
candidate prognostic biomarker but do not establish cGAS as a predictor of chemotherapy response or as a causal
driver of treatment resistance.
- Faculty
- Faculté des sciences et de médecine
- Department
- Section de médecine
- Language
-
- English
- Classification
- Pathology, clinical medicine
- Other electronic version
- License
-
CC BY-NC-ND
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.lungcan.2026.109553
- ISSN 0169-5002
- Persistent URL
- https://folia.unifr.ch/unifr/documents/336387
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