Application of Proteomics to Soft Tissue Sarcomas
Posted: Sun Feb 07, 2016 12:21 pm
Been reading on Nano sciences and studies
This aricle gives light to why sarcomas are hard to gage for protein contents in sarcoma patients but gives us yet another chance of finding a cure through cell studies and cancer collaborations.
We all need to unite world wide to beat ASPS
Int J Proteomics. 2012; 2012: 876401.
Published online 2012 Jun 19. doi: 10.1155/2012/876401
PMCID: PMC3388341
Application of Proteomics to Soft Tissue Sarcomas
Tadashi Kondo, 1 ,* Daisuke Kubota, 1 and Akira Kawai 2
Author information ► Article notes ► Copyright and License information ►
Abstract
Soft tissue sarcomas are rare and account for less than 1% of all malignant cancers. Other than development of intensive therapies, the clinical outcome of patients with soft tissue sarcoma remains very poor, particularly when diagnosed at a late stage. Unique mutations have been associated with certain soft tissue sarcomas, but their etiologies remain unknown. The proteome is a functional translation of a genome, which directly regulates the malignant features of tumors. Thus, proteomics is a promising approach for investigating soft tissue sarcomas. Various proteomic approaches and clinical materials have been used to address clinical and biological issues, including biomarker development, molecular target identification, and study of disease mechanisms. Several cancer-associated proteins have been identified using conventional technologies such as 2D-PAGE, mass spectrometry, and array technology. The functional backgrounds of proteins identified were assessed extensively using in vitro experiments, thus supporting expression analysis. These observations demonstrate the applicability of proteomics to soft tissue sarcoma studies. However, the sample size in each study was insufficient to allow conclusive results. Given the low frequency of soft tissue sarcomas, multi-institutional collaborations are required to validate the results of proteomic approaches.
2.13. Alveolar Soft Part Sarcoma (ASPS)
ASPS is a rare tumor that generally occurs in soft tissues of the extremities of young adults [138]. ASPS diagnostic histology includes a nest-like or organoid pattern separated by fibrovascular septa [138]. However, diagnosis of ASPS in an unusual location, such as the lung, stomach, retroperitoneum, and female genital tract may be difficult because a number of more common tumors mimic the histological features of ASPS [139]. Distinctive periodic acid-Schiff-positive crystals are another classical histological feature of ASPS [140], but typical crystals are observed only in a limited number of ASPS cases [138]. The detection of an ASPSCR1-TFE3 fusion transcript by RT-PCR is considered to be a marker of ASPS, but novel markers for immunohistochemical study are also required [141].
Balgley et al. compared the protein content of ASPS with uterine leiomyoma to identify a diagnostic protein biomarker for ASPS [142]. This study also aimed to assess the potential of formalin-fixed and paraffin-embedded (FFPE) tissue specimens for proteomic studies after long-term storage for several decades. Proteins were extracted from FFPE tissue specimens of tumors, digested with trypsin, and examined by combined capillary isoelectric focusing/nanoreversed phase liquid chromatography separation coupled with electrospray ionization—MS. Of the 2583 proteins identified, 80 were uniquely observed in ASPS. Immunohistochemistry confirmed the unique expression of vacuolar proton translocating ATPase 116 kDa subunit isoform a3.
It was interesting that proteomic study was feasible for samples that had been stored for several decades as FFPE. The application of FFPE to cancer proteomics has been examined for other malignancies, including ASPS. ASPS is particularly rare compared with other soft tissue sarcomas, and hence, the use of FFPE would be more valuable in ASPS. The diagnostic value of vacuolar proton translocating ATPase 116 kDa subunit isoform a3 should be validated with a large sample set, in parallel with functional assessments. Separation by capillary isoelectric focusing prior to LC-MS/MS was also a unique point of this study
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388341/
http://proteomics.cancer.gov/whatisproteomics
This aricle gives light to why sarcomas are hard to gage for protein contents in sarcoma patients but gives us yet another chance of finding a cure through cell studies and cancer collaborations.
We all need to unite world wide to beat ASPS
Int J Proteomics. 2012; 2012: 876401.
Published online 2012 Jun 19. doi: 10.1155/2012/876401
PMCID: PMC3388341
Application of Proteomics to Soft Tissue Sarcomas
Tadashi Kondo, 1 ,* Daisuke Kubota, 1 and Akira Kawai 2
Author information ► Article notes ► Copyright and License information ►
Abstract
Soft tissue sarcomas are rare and account for less than 1% of all malignant cancers. Other than development of intensive therapies, the clinical outcome of patients with soft tissue sarcoma remains very poor, particularly when diagnosed at a late stage. Unique mutations have been associated with certain soft tissue sarcomas, but their etiologies remain unknown. The proteome is a functional translation of a genome, which directly regulates the malignant features of tumors. Thus, proteomics is a promising approach for investigating soft tissue sarcomas. Various proteomic approaches and clinical materials have been used to address clinical and biological issues, including biomarker development, molecular target identification, and study of disease mechanisms. Several cancer-associated proteins have been identified using conventional technologies such as 2D-PAGE, mass spectrometry, and array technology. The functional backgrounds of proteins identified were assessed extensively using in vitro experiments, thus supporting expression analysis. These observations demonstrate the applicability of proteomics to soft tissue sarcoma studies. However, the sample size in each study was insufficient to allow conclusive results. Given the low frequency of soft tissue sarcomas, multi-institutional collaborations are required to validate the results of proteomic approaches.
2.13. Alveolar Soft Part Sarcoma (ASPS)
ASPS is a rare tumor that generally occurs in soft tissues of the extremities of young adults [138]. ASPS diagnostic histology includes a nest-like or organoid pattern separated by fibrovascular septa [138]. However, diagnosis of ASPS in an unusual location, such as the lung, stomach, retroperitoneum, and female genital tract may be difficult because a number of more common tumors mimic the histological features of ASPS [139]. Distinctive periodic acid-Schiff-positive crystals are another classical histological feature of ASPS [140], but typical crystals are observed only in a limited number of ASPS cases [138]. The detection of an ASPSCR1-TFE3 fusion transcript by RT-PCR is considered to be a marker of ASPS, but novel markers for immunohistochemical study are also required [141].
Balgley et al. compared the protein content of ASPS with uterine leiomyoma to identify a diagnostic protein biomarker for ASPS [142]. This study also aimed to assess the potential of formalin-fixed and paraffin-embedded (FFPE) tissue specimens for proteomic studies after long-term storage for several decades. Proteins were extracted from FFPE tissue specimens of tumors, digested with trypsin, and examined by combined capillary isoelectric focusing/nanoreversed phase liquid chromatography separation coupled with electrospray ionization—MS. Of the 2583 proteins identified, 80 were uniquely observed in ASPS. Immunohistochemistry confirmed the unique expression of vacuolar proton translocating ATPase 116 kDa subunit isoform a3.
It was interesting that proteomic study was feasible for samples that had been stored for several decades as FFPE. The application of FFPE to cancer proteomics has been examined for other malignancies, including ASPS. ASPS is particularly rare compared with other soft tissue sarcomas, and hence, the use of FFPE would be more valuable in ASPS. The diagnostic value of vacuolar proton translocating ATPase 116 kDa subunit isoform a3 should be validated with a large sample set, in parallel with functional assessments. Separation by capillary isoelectric focusing prior to LC-MS/MS was also a unique point of this study
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388341/
To follow an excellent link to use for research on the benefits of refining and being able to have science apply the research for drug development to fight ASPS and other cancers.What is Cancer Proteomics?
The term "proteome" refers to the entire complement of proteins, including the modifications made to a particular set of proteins, produced by an organism or a cellular system. This will vary with time and distinct requirements, such as stresses, that a cell or organism undergoes. The term "proteomics" is a large-scale comprehensive study of a specific proteome, including information on protein abundances, their variations and modifications, along with their interacting partners and networks, in order to understand cellular processes. “Clinical proteomics” is a sub-discipline of proteomics that involves the application of proteomic technologies on clinical specimens such as blood. Cancer, in particular, is a model disease for applying such technologies to identify unique biosignatures and biomarkers responsible for the diagnosis, prognosis and therapeutic prediction of such disease. Biomarkers are biological molecules found in blood, other body fluids, or tissues that are a sign of a normal or abnormal process, or of a condition or disease. They may also be used to see how well the body responds to a treatment for a disease or condition.
http://proteomics.cancer.gov/whatisproteomics