Organism Stability Disruption as a Decomposable Tumor Repair-State Axis

Organism Stability Disruption as a Decomposable Tumor Repair-State Axis Background and Objective Cancer is commonly understood through genetic alterations, uncontrolled proliferation, immune evasion, metabolic adaptation and tumor microenvironment remodeling. This research investigates an additional systems-level perspective: whether malignant tissue can exhibit a pathologically stabilized repair-like state characterized by persistent inflammatory signaling, extracellular matrix remodeling, hypoxia, stress tolerance and incomplete restoration of tissue homeostasis. The study introduces Organism Stability Disruption (OSD) as a measurable, decomposable tissue-state framework. OSD is defined through the balance between biological instability modules and order-capacity modules, with additional adjustment for proliferation. Methods The framework was evaluated through retrospective computational analyses of publicly available molecular and clinical datasets, including TCGA/GTEx, TCGA PanCancer Atlas, CPTAC, DepMap, PRISM, LINCS/L1000 and IMvigor210. The analyses incorporate survival modeling, biological comparator adjustment, cross-validation, permutation testing, transcriptomic and proteogenomic comparisons, single-cell heterogeneity assessments, and perturbation-based hypothesis prioritization. Principal Findings In TCGA/GTEx comparisons, raw OSD was elevated in tumor samples across 11 of 13 tissue sites, and residual OSD remained elevated in 9 of 13 sites after adjustment for proliferation. Among 8,893 TCGA primary tumors with survival annotations, higher residual OSD was associated with worse overall survival in a cancer-type-stratified Cox model (HR = 1.110 per standard deviation; p = 1.50 × 10⁻⁷). Additional analyses identified incremental prognostic information beyond selected biological comparator signatures, while confirming substantial heterogeneity between cancer types. Independent treatment-response analyses demonstrated that OSD should not be interpreted as a universal immunotherapy-response biomarker. Instead, individual biological components, particularly wound/ECM remodeling and hypoxia/redox stress, showed context-dependent associations. Scientific Contribution and Future Validation The study develops OSD as a quantitative framework for investigating pathological repair-state stabilization in cancer. It connects retrospective molecular and clinical observations with a falsifiable experimental hypothesis involving perturbation, withdrawal, recovery and rechallenge. A separate preclinical laboratory protocol specifies experimental controls, molecular readouts, statistical decision criteria and conditions for independent replication. Research Status This work presents retrospective computational findings and proposed experimental validation procedures. The results do not establish a universal cancer biomarker, demonstrate causal tumor-state resetting, prove clinical efficacy or constitute a cancer treatment recommendation. Related research protocol: https://doi.org/10.5281/zenodo.23247433