• Author
    Jim Yee
  • Discovery PI

    Dr. Sriram Eleswarapu & Dr. Juan Andino

  • Project Co-Author

    Dr. Istvan Kovanecz, Ahmed Elauri

  • Abstract Title

    Proteomic Atlas of Estrogen-Exposed Human Penile Tunica Albuginea

  • Discovery AOC Petal or Dual Degree Program

    Informatics & Data Science

  • Abstract

    Background: The tunica albuginea (TA) is essential for penile rigidity and veno-occlusion, but human molecular characterization remains sparse and no prior human discovery-proteomics atlas was identified.

    Objective: To define the proteomic landscape of estrogen-exposed human penile TA.

    Methods: TA from 8 transgender women undergoing gender-affirming penectomy after feminizing hormone exposure underwent bottom-up label-free quantitative proteomics in the reported FragPipe/DIA-NN workflow. Protein abundance, rank, and inter-specimen reproducibility were summarized, with focused review of extracellular-matrix, smooth-muscle, metabolic, and estrogen-responsive proteins.

    Outcomes: Primary outcomes were protein detection, relative abundance ranking, and reproducibility across specimens.

    Results: A total of 6,588 proteins were quantified with a median coefficient of variation of 5.1%; 76% had CV <10%, and 7% (452/6,588) had CV >15%. Fourteen collagen chains spanning 8 collagen types were detected. COL12A1 isoform 1 was the most abundant collagen (mean log2 intensity 24.97; rank 7), followed by COL12A1 isoform 2 (24.05; rank 17), both exceeding COL1A2 (23.09; rank 35) and COL1A1 (22.58; rank 44). Relative to COL1A2 and COL1A1, COL12A1 isoform 1 was higher by 1.88 and 2.39 log2 units, respectively, equivalent to approximately 3.7-fold and 5.2-fold higher relative abundance. FBN1 ranked 47th overall (22.48), ELN was sparse (11.0; CV 14.5%), and LOXL2 exceeded LOX (18.74 vs 12.44). MYH11 (22.64; rank 41; CV 2.8%), CNN1 (21.42; CV 3.3%), and TAGLN (16.38; CV 1.8%) were detected, whereas ACTA2 and DES were not. Seven of 14 estrogen-responsive markers were detected, including CTSD (17.87; CV 1.1%) and IGFBP4 (19.13; CV 5.1%), while ESR1, ESR2, and GPER1 were not detected.

    Conclusions: The current dataset supports a conservative atlas-style paper describing a COL12A1-rich collagen network, fibrillin-dominant elastic architecture, and an exploratory MYH11-positive, ACTA2-non-detected smooth-muscle signature.

    Clinical Implications: These data provide a molecular reference for Peyronie’s disease biology and TA tissue engineering.

    Limitations: The study is small, lacks a non-estrogen-exposed comparator and orthogonal validation, and cannot equate receptor non-detection with true absence; peptide-level support, hormone-regimen metadata, and pathologist-verified tissue purity were not available in the current files.

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