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Multi-modal characterization of metabolic and immune gene clusters in adrenocortical carcinoma treatment
Wenjun Hao1,2,3,4, Luhan Yao5, Yanlong Wang1,2,3,4
1Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Abstract:
Adrenocortical carcinoma (ACC) is an uncommon and aggressive endocrine malignancy, characterized by limited therapeutic options and considerable variability in patient outcomes. The challenge is to combine the complex information of ACC with artificial intelligence (AI) and clinical and pathology data to achieve precision medicine and improve patient prognosis. We developed the Steroid-related Immune Score (SIS) using multi-modal analysis of genomics, digital pathology, and artificial intelligence and validated it in external datasets. In addition, we conducted single-cell RNA sequencing (scRNA-seq) of small samples and in vitro functional experiments. SIS delivered a stable performance with an AUC of 0.8 ± 0.01 in the ResNet50 and Vision Transformer-B16 models. We validated the best model in external ACC cohorts. Using Class Activation Maps (CAMs) technology revealed that SIS was associated with lymphocyte infiltration, establishing it as a new feature in addition to the Weiss scoring system. Patients in the high SIS group responded well to immunotherapy, while the low SIS group showed adaptability to hormone inhibition therapy. Single-cell RNA sequencing data revealed the relationship between the tumor microenvironment and drug resistance in ACC. In vitro functional assays demonstrated that elevated DHCR7 gene expression correlated with unfavorable prognosis and treatment sensitivity, identifying it as a prospective therapeutic target. Furthermore, there are similarities between the metabolic characteristics of ACC and schizophrenia, such as calcium and iron ion levels. Our multi-modal analysis comprehensively characterizes the immune microenvironment of ACC, emphasizing the synergistic regulation of metabolic and immune gene clusters that influence ACC patients' responses to immune and hormone therapies.
Insights
A novel Steroid-related Immune Score (SIS) integrates genomics, pathology, and AI for Adrenocortical carcinoma (ACC). This score predicts treatment response, guiding precision medicine for better patient outcomes.
Area of Science:
- Endocrinology
- Oncology
- Artificial Intelligence
- Genomics
- Digital Pathology
Background:
- Adrenocortical carcinoma (ACC) is a rare, aggressive endocrine cancer with poor prognosis and limited treatment options.
- Integrating complex multi-modal data (genomics, pathology, AI) is crucial for advancing precision medicine in ACC.
- Current prognostic and therapeutic strategies for ACC require enhancement to improve patient outcomes.
Purpose of the Study:
- To develop and validate a multi-modal AI-driven score (Steroid-related Immune Score - SIS) for Adrenocortical carcinoma (ACC).
- To characterize the immune microenvironment of ACC and its relationship with therapeutic response.
- To identify novel therapeutic targets and understand metabolic similarities with other conditions.
Main Methods:
- Multi-modal analysis integrating genomics, digital pathology, and artificial intelligence (AI) to develop the SIS.
- Validation of the SIS model using external Adrenocortical carcinoma (ACC) cohorts.
- Single-cell RNA sequencing (scRNA-seq) and in vitro functional experiments to investigate tumor microenvironment and gene expression.
- Class Activation Maps (CAMs) technology for visualizing SIS associations with tumor features.
Main Results:
- The Steroid-related Immune Score (SIS) demonstrated robust performance (AUC 0.8 ± 0.01) in predicting outcomes.
- SIS is associated with lymphocyte infiltration, serving as a novel prognostic marker beyond the Weiss score.
- High SIS predicts immunotherapy response; low SIS suggests suitability for hormone inhibition therapy.
- DHCR7 gene expression is linked to poor prognosis and treatment sensitivity in Adrenocortical carcinoma (ACC).
- Metabolic similarities, including ion levels, were observed between Adrenocortical carcinoma (ACC) and schizophrenia.
Conclusions:
- The Steroid-related Immune Score (SIS) offers a powerful tool for precision medicine in Adrenocortical carcinoma (ACC), guiding treatment selection.
- Multi-modal AI analysis comprehensively characterizes the Adrenocortical carcinoma (ACC) immune microenvironment and its role in therapy response.
- DHCR7 presents a potential therapeutic target, and understanding metabolic-immune interactions is key to improving Adrenocortical carcinoma (ACC) patient prognosis.
