Mass Spectrometric Identification of Ancient Proteins as Potential Molecular Biomarkers for a 2000-Year-Old Osteogenic Sarcoma

Bóna, Ágnes; Papai, Zoltan; Maász, Gábor; Tóth, Gábor; Jámbor, Éva; Schmidt, J.; Tóth, Csaba; Farkas, Csilla; Mark, Laszlo

doi:10.1371/journal.pone.0087215

Cited by 32 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, ancient proteins have revealed past diseases such as osteogenic sarcoma and prostate carcinoma [17,79]. Scott et al [80] reported that osteocalcin analysis is promising for detecting stress.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of archaeological human bone

et al. 2017

View full text Add to dashboard Cite

Ancient protein analysis provides clues to human life and diseases from ancient times. Here, we performed shotgun proteomics of human archeological bones for the first time, using rib bones from the Hitotsubashi site (AD 1657–1683) in Tokyo, called Edo in ancient times. The output data obtained were analysed using Gene Ontology and label-free quantification. We detected leucocyte-derived proteins, possibly originating from the bone marrow of the rib. Particularly prevalent and relatively high expression of eosinophil peroxidase suggests the influence of infectious diseases. This scenario is plausible, considering the overcrowding and unhygienic living conditions of the Edo city described in the historical literature. We also observed age-dependent differences in proteome profiles, particularly for proteins involved in developmental processes. Among them, alpha-2-HS-glycoprotein demonstrated a strong negative correlation with age. These results suggest that analysis of ancient proteins could provide a useful indicator of stress, disease, starvation, obesity and other kinds of physiological and pathological information.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of archaeological human bone

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Western blotting detected prostate-specific antigen in bone from an ancient specimen with metastatic prostate cancer (23). Proteomic analysis of a 2,000-y-old bone tumor identified several contemporary biomarkers (24). These proteins contain an additional level of information that offers opportunities for exploring the history and evolution of disease, potentially even through the detection of mutations or modifications within protein sequences (25).…”

mentioning

confidence: 99%

Molecular insights into an ancient form of Paget’s disease of bone

Shaw

Burrell

Green

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Paget’s disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y of age. PDB-like changes have been reported in archaeological remains as old as Roman, although accurate diagnosis and natural history of the disease is lacking. Six skeletons from a collection of 130 excavated at Norton Priory in the North West of England, which dates to medieval times, show atypical and extensive pathological changes resembling contemporary PDB affecting as many as 75% of individual skeletons. Disease prevalence in the remaining collection is high, at least 16% of adults, with age at death estimations as low as 35 y. Despite these atypical features, paleoproteomic analysis identified sequestosome 1 (SQSTM1) or p62, a protein central to the pathological milieu of PDB, as one of the few noncollagenous human sequences preserved in skeletal samples. Targeted proteomic analysis detected >60% of the ancient p62 primary sequence, with Western blotting indicating p62 abnormalities, including in dentition. Direct sequencing of ancient DNA excluded contemporary PDB-associated SQSTM1 mutations. Our observations indicate that the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated domain. Ancient miRNAs were remarkably preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression consistent with that reported in contemporary PDB-associated bone tumors. Our work displays the use of proteomics to inform diagnosis of ancient diseases such as atypical PDB, which has unusual features presumably potentiated by yet-unidentified environmental or genetic factors.

show abstract

“…A typical disease responsible for the development of osteoblastic bone tumors could be a representative primary malignant bone tumor, such as osteosarcoma. Smith-Guzman [ 2 ] reported a case of primary malignant bone tumor observed in the right humerus excavated from a Pre - Columbian era ruin from A.D. 1265–1380, Aufderheide [ 3 ] reported a case of osteosarcoma showing a typical sunburst appearance, which developed in the distal humerus and femur in an adult native Peruvian 800 years ago, and Bona [ 4 ] reported the results of an investigation of osteosarcoma in the right humerus using a biomarker in a 25–35-year-old female excavated from an approximately 2,000-year-old ruin. All these cases developed in a solitary bone.…”

Section: Discussionmentioning

confidence: 99%

An Ancient Skeleton with Multiple Osteoblastic Bone Lesions Containing a Scapular Sunburst Appearance from a 5th–6th Century Grave Excavated in Oita, Japan

Tsurumoto

Wakebe

Ogami-Takamura

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

A human skeleton of a middle-aged adult male was found in a 5th–6th century Kinoue-Kodo stone coffin excavated from the southwest marginal region of the Oita plains, northeast Kyushu, Japan. The skeleton was buried respectfully in the ancient tomb, and red pigment was applied to his face after death. We report herein findings from computed tomography imaging of the skeleton and discuss the multiple osteoblastic lesions identified in the humerus, scapula, clavicle, vertebra, pelvic bones, and skull of this individual. These lesions comprised cortical bone thickening with periosteal reaction localized to the surface and osteosclerotic changes mainly observed in the trabecular structure of cancellous bone. In particular, a typical sunburst pattern was also noted on the left scapula as another characteristic lesion found in this case. By differential diagnosis, the disease suffered by this individual was most likely to be metastatic bone tumors, especially of prostate cancer. This person may have survived until many bone metastases had developed throughout his whole body.

show abstract

Mass Spectrometric Identification of Ancient Proteins as Potential Molecular Biomarkers for a 2000-Year-Old Osteogenic Sarcoma

Cited by 32 publications

References 36 publications

Proteomic profiling of archaeological human bone

Proteomic profiling of archaeological human bone

Molecular insights into an ancient form of Paget’s disease of bone

An Ancient Skeleton with Multiple Osteoblastic Bone Lesions Containing a Scapular Sunburst Appearance from a 5th–6th Century Grave Excavated in Oita, Japan

Contact Info

Product

Resources

About