Solid Tumors Pan Cancer Transcriptome: Tissue/Cancer specific expression groups at the Isoform-Level

Area of Science:

• Genomics and Transcriptomics
• Cancer Biology
• Bioinformatics

Background:

• The human genome transcribes into diverse isoforms, with tissue-specific expression often disrupted in cancer.
• Isoform-level dysregulation in solid tumors remains poorly understood, limiting diagnostic and therapeutic applications.
• Existing cancer-testis antigen (CTA) databases are incomplete, missing many potential tumor biomarkers.

Purpose of the Study:

• To systematically classify transcript expression across solid tumors and normal tissues using an isoform-centric approach.
• To identify novel diagnostic biomarkers and unannotated CTAs through pan-cancer transcriptome analysis.
• To develop accurate isoform signatures for stratifying glioma subtypes and enabling precision oncology.

Main Methods:

• Development and application of STPCaT (Solid Tumors Pan-Cancer Transcriptome) analysis, extending TransTEx.
• Classification of transcript expression across TCGA solid tumors and GTEx normal tissues.
• Consensus clustering and random-forest feature selection for identifying discriminative isoform signatures in pan-gliomas.

Main Results:

• STPCaT revealed a collapse of normal tissue-specific expression programs in cancer, with two dominant isoform groups: cancer-high and normal-high.
• A significant repertoire of previously unannotated CTAs was discovered, many relevant across multiple cancers, including gliomas.
• Highly accurate (97-98%) isoform signatures for stratifying low-grade gliomas and glioblastomas were identified using as few as five transcripts.

Conclusions:

• STPCaT provides a scalable, isoform-resolved resource for advancing tumor stratification and biomarker discovery in solid tumors.
• The identified isoform signatures offer potential for precision oncology applications, particularly in glioma subtyping.
• The study highlights the critical role of isoform-level analysis in understanding cancer biology and uncovering novel therapeutic targets.