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CREBench: Evaluating Large Language Models in Cryptographic Binary Reverse Engineering

arXiv:2604.03750v1 Announce Type: cross Abstract: Reverse engineering (RE) is central to software security, particularly for cryptographic programs that handle sensitive data and are highly prone to vulnerabilities. It supports critical tasks such as vulnerability discovery and malware analysis. Despite its importance, RE remains labor-intensive and requires substantial expertise, making large language models (LLMs) a potential solution for automating the process. However, their capabilities for RE remain systematically underexplored. To address this gap, we study the cryptographic binary RE capabilities of LLMs and introduce \textbf{CREBench}, a benchmark comprising 432 challenges built from 48 standard cryptographic algorithms, 3 insecure crypto key usage scenarios, and 3 difficulty levels. Each challenge follows a Capture-the-Flag (CTF) RE challenge, requiring the model to analyze the underlying cryptographic logic and recover the correct input. We design an evaluation framework comprising four sub-tasks, from algorithm identification to correct flag recovery. We evaluate eight frontier LLMs on CREBench. GPT-5.4, the best-performing model, achieves 64.03 out of 100 and recovers the flag in 59\% of challenges. We also establish a strong human expert baseline of 92.19 points, showing that humans maintain an advantage in cryptographic RE tasks. Our code and dataset are available at https://github.com/wangyu-ovo/CREBench.
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Integrative Multi-Omics and Single-Cell Analysis Reveal THOC3 and THOC7 as Oncogenic RNA Processing Regulators in Lung Adenocarcinoma

Int J Med Sci. 2026 Mar 9;23(4):1408-1430. doi: 10.7150/ijms.128975. eCollection 2026.

ABSTRACT

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Although the transcription-export (TREX) complex plays a central role in RNA maturation and nuclear export, the clinical and biological relevance of individual THO Complex Subunit (including THOC1, THOC2, THOC3, THOC5, THOC6, and THOC7) in LUAD is not well defined. We performed integrative analyses combining bulk transcriptomics from TCGA/GTEx and independent GEO cohorts, survival modeling, DNA methylation profiling, protein-level annotation from public resources, protein-protein interaction network analysis, immune infiltration estimation (TIMER), and single-cell RNA sequencing (scRNA-seq) to evaluate the relevance of THOC3 and THOC7 in LUAD. Across TCGA and external GEO validation datasets, THOC3 and THOC7 were consistently upregulated in LUAD and associated with poorer overall and disease-free survival, whereas other THO complex members showed weaker or inconsistent associations. Given these comparatively consistent and reproducible signals, we therefore prioritized THOC3 and THOC7 for downstream multi-layer analyses. Epigenetic profiling and interaction network analyses placed both genes within conserved RNA processing and export programs linked to genome maintenance pathways. Single-cell transcriptomic analysis provided additional resolution, demonstrating predominant enrichment of THOC3 and THOC7 in malignant epithelial clusters, with THOC3 aligning with transcriptional programs associated with DNA replication and repair, and THOC7 with proliferative and checkpoint-related states. Notably, expression of both genes was also detectable in myeloid and neutrophil subsets, and THOC7 expression remained elevated in recurrent LUAD samples, indicating association with aggressive and treatment-resistant disease states. Collectively, by integrating bulk, single-cell, epigenetic, and immune profiling across multiple independent cohorts, this study identifies THOC3 and THOC7 as reproducible molecular correlates of aggressive LUAD phenotypes. These highlight dysregulated RNA export programs as potential biomarkers of poor prognosis and motivate future functional studies to assess RNA export dependencies in LUAD.

PMID:41938520 | PMC:PMC13048885 | DOI:10.7150/ijms.128975

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Integrative Multi-Omics and Single-Cell Analysis Reveal THOC3 and THOC7 as Oncogenic RNA Processing Regulators in Lung Adenocarcinoma

Int J Med Sci. 2026 Mar 9;23(4):1408-1430. doi: 10.7150/ijms.128975. eCollection 2026.

ABSTRACT

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Although the transcription-export (TREX) complex plays a central role in RNA maturation and nuclear export, the clinical and biological relevance of individual THO Complex Subunit (including THOC1, THOC2, THOC3, THOC5, THOC6, and THOC7) in LUAD is not well defined. We performed integrative analyses combining bulk transcriptomics from TCGA/GTEx and independent GEO cohorts, survival modeling, DNA methylation profiling, protein-level annotation from public resources, protein-protein interaction network analysis, immune infiltration estimation (TIMER), and single-cell RNA sequencing (scRNA-seq) to evaluate the relevance of THOC3 and THOC7 in LUAD. Across TCGA and external GEO validation datasets, THOC3 and THOC7 were consistently upregulated in LUAD and associated with poorer overall and disease-free survival, whereas other THO complex members showed weaker or inconsistent associations. Given these comparatively consistent and reproducible signals, we therefore prioritized THOC3 and THOC7 for downstream multi-layer analyses. Epigenetic profiling and interaction network analyses placed both genes within conserved RNA processing and export programs linked to genome maintenance pathways. Single-cell transcriptomic analysis provided additional resolution, demonstrating predominant enrichment of THOC3 and THOC7 in malignant epithelial clusters, with THOC3 aligning with transcriptional programs associated with DNA replication and repair, and THOC7 with proliferative and checkpoint-related states. Notably, expression of both genes was also detectable in myeloid and neutrophil subsets, and THOC7 expression remained elevated in recurrent LUAD samples, indicating association with aggressive and treatment-resistant disease states. Collectively, by integrating bulk, single-cell, epigenetic, and immune profiling across multiple independent cohorts, this study identifies THOC3 and THOC7 as reproducible molecular correlates of aggressive LUAD phenotypes. These highlight dysregulated RNA export programs as potential biomarkers of poor prognosis and motivate future functional studies to assess RNA export dependencies in LUAD.

PMID:41938520 | PMC:PMC13048885 | DOI:10.7150/ijms.128975

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