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Identification of plasma protein markers common to patients with malignant tumour and Abnormal Savda in Uighur medicine: a prospective clinical study.

Upur H, Chen Y, Kamilijiang M, Deng W, Sulaiman X, Aizezi R, Wu X, Tulake W, Abudula A - BMC Complement Altern Med (2015)

Bottom Line: We identified 31 plasma proteins that were differentially expressed in ASt compared with nASt, of which only 10 showed quantitatively different expression between ASt and NC.ELISA detection showed significant upregulation of plasma SAA1 and SPP24 and downregulation of PIGR and FASN in ASt compared with nASt and NC (p < 0.05).Abnormal Savda may be causally associated with changes in the whole regulation network of protein expression during carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of High-Incident Diseases in Uyghur Ethnic Population supported by the Chinese Ministry of Education, Xinjiang Medical University, 393 Xinyi Rd., Urumqi, 830011, P R China. halmurat@263.net.

ABSTRACT

Background: Traditional Uighur medicine shares an origin with Greco-Arab medicine. It describes the health of a human body as the dynamic homeostasis of four normal Hilits (humours), known as Kan, Phlegm, Safra, and Savda. An abnormal change in one Hilit may cause imbalance among the Hilits, leading to the development of a syndrome. Abnormal Savda is a major syndrome of complex diseases that are associated with common biological changes during disease development. Here, we studied the protein expression profile common to tumour patients with Abnormal Savda to elucidate the biological basis of this syndrome and identify potential biomarkers associated with Abnormal Savda.

Methods: Patients with malignant tumours were classified by the diagnosis of Uighur medicine into two groups: Abnormal Savda type tumour (ASt) and non-Abnormal Savda type tumour (nASt), which includes other syndromes. The profile of proteins that were differentially expressed in ASt compared with nASt and normal controls (NC) was analysed by iTRAQ proteomics and evaluated by bioinformatics using MetaCore™ software and an online database. The expression of candidate proteins was verified in all plasma samples by enzyme-linked immunosorbent assay (ELISA).

Results: We identified 31 plasma proteins that were differentially expressed in ASt compared with nASt, of which only 10 showed quantitatively different expression between ASt and NC. Bioinformatics analysis indicated that most of these proteins are known biomarkers for neoplasms of the stomach, breast, and lung. ELISA detection showed significant upregulation of plasma SAA1 and SPP24 and downregulation of PIGR and FASN in ASt compared with nASt and NC (p < 0.05).

Conclusions: Abnormal Savda may be causally associated with changes in the whole regulation network of protein expression during carcinogenesis. The expression of potential biomarkers might be used to distinguish Abnormal Savda from other syndromes.

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Related in: MedlinePlus

The role and function of proteins associated with Abnormal Savda type tumours (ASt) in biological processes as displayed by MetaCore™ analysis (p< 0.05). The analysis includes the function of 31 proteins described in Table 1.
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Fig1: The role and function of proteins associated with Abnormal Savda type tumours (ASt) in biological processes as displayed by MetaCore™ analysis (p< 0.05). The analysis includes the function of 31 proteins described in Table 1.

Mentions: The role of the 31 identified proteins that differentiate ASt from nASt in disease development or tumourigenesis was further evaluated by bioinformatics analysis using MetaCore™ software (version 6.16) and an online database (http://www.genego.com). Gene Ontology analysis showed that most of these proteins are localized in the extracellular space, and only small proportions are present at the membrane or in the cytoplasm. These proteins are main players in protein binding or function in the negative regulation of endopeptidase or phospholipase activity, positive regulation of macrophage or platelet activation, and the regulation of acute-phase and inflammatory responses (Figure 1). Some proteins are important regulators of signalling networks or pathways, such as blood coagulation, immune response by multiple TLR signalling, regulation of glucose and lipid metabolism, cell adhesion, transcriptional regulation, or function as effectors in receptor signalling (data not shown). Biomarker Assessment analysis based on the Disease Ontology database identified most of the proteins as potential biomarkers that had previously been described in other studies. Among them, 17 proteins are involved in stomach disease or neoplasm (P04083, P02649, P49327, P02671, P02679, P06396, P10809, Q12794, P17936, P20742, P02753, P02735, P02735, P35542, P01011, P07996, and P04275) and 22 are potential biomarkers for breast disease and neoplasm, in particular five proteins (P07996, P10809, P17936, Q16610, and Q12794) for breast ductal carcinoma, one (P17936) for hereditary breast cancer, and one (P01011) for fibrocystic breast disease. All proteins except one (A6NMY6) are involved in lung disease or neoplasm, particularly 14 proteins (P01833, P02735, P02649, P02763, P04275, P02679, P06396, P07996, P10809, P17936, P36955, P62753, Q06033, and Q12794) in bronchial neoplasm, three (P17936, P02763, and P62753) in small cell lung carcinoma, and 12 (P02649, P02679, P02735, P04275, P06396, P07996, P10809, Q12794, P17936, P36955, and P62753) in non-small cell lung carcinoma. These findings suggest that the development of Abnormal Savda in tumour patients is probably associated with dysregulation of a whole protein interaction network, and is mainly manifested in aberrant expression of potential biomarkers for malignant tumours.Figure 1


Identification of plasma protein markers common to patients with malignant tumour and Abnormal Savda in Uighur medicine: a prospective clinical study.

Upur H, Chen Y, Kamilijiang M, Deng W, Sulaiman X, Aizezi R, Wu X, Tulake W, Abudula A - BMC Complement Altern Med (2015)

The role and function of proteins associated with Abnormal Savda type tumours (ASt) in biological processes as displayed by MetaCore™ analysis (p< 0.05). The analysis includes the function of 31 proteins described in Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4321703&req=5

Fig1: The role and function of proteins associated with Abnormal Savda type tumours (ASt) in biological processes as displayed by MetaCore™ analysis (p< 0.05). The analysis includes the function of 31 proteins described in Table 1.
Mentions: The role of the 31 identified proteins that differentiate ASt from nASt in disease development or tumourigenesis was further evaluated by bioinformatics analysis using MetaCore™ software (version 6.16) and an online database (http://www.genego.com). Gene Ontology analysis showed that most of these proteins are localized in the extracellular space, and only small proportions are present at the membrane or in the cytoplasm. These proteins are main players in protein binding or function in the negative regulation of endopeptidase or phospholipase activity, positive regulation of macrophage or platelet activation, and the regulation of acute-phase and inflammatory responses (Figure 1). Some proteins are important regulators of signalling networks or pathways, such as blood coagulation, immune response by multiple TLR signalling, regulation of glucose and lipid metabolism, cell adhesion, transcriptional regulation, or function as effectors in receptor signalling (data not shown). Biomarker Assessment analysis based on the Disease Ontology database identified most of the proteins as potential biomarkers that had previously been described in other studies. Among them, 17 proteins are involved in stomach disease or neoplasm (P04083, P02649, P49327, P02671, P02679, P06396, P10809, Q12794, P17936, P20742, P02753, P02735, P02735, P35542, P01011, P07996, and P04275) and 22 are potential biomarkers for breast disease and neoplasm, in particular five proteins (P07996, P10809, P17936, Q16610, and Q12794) for breast ductal carcinoma, one (P17936) for hereditary breast cancer, and one (P01011) for fibrocystic breast disease. All proteins except one (A6NMY6) are involved in lung disease or neoplasm, particularly 14 proteins (P01833, P02735, P02649, P02763, P04275, P02679, P06396, P07996, P10809, P17936, P36955, P62753, Q06033, and Q12794) in bronchial neoplasm, three (P17936, P02763, and P62753) in small cell lung carcinoma, and 12 (P02649, P02679, P02735, P04275, P06396, P07996, P10809, Q12794, P17936, P36955, and P62753) in non-small cell lung carcinoma. These findings suggest that the development of Abnormal Savda in tumour patients is probably associated with dysregulation of a whole protein interaction network, and is mainly manifested in aberrant expression of potential biomarkers for malignant tumours.Figure 1

Bottom Line: We identified 31 plasma proteins that were differentially expressed in ASt compared with nASt, of which only 10 showed quantitatively different expression between ASt and NC.ELISA detection showed significant upregulation of plasma SAA1 and SPP24 and downregulation of PIGR and FASN in ASt compared with nASt and NC (p < 0.05).Abnormal Savda may be causally associated with changes in the whole regulation network of protein expression during carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of High-Incident Diseases in Uyghur Ethnic Population supported by the Chinese Ministry of Education, Xinjiang Medical University, 393 Xinyi Rd., Urumqi, 830011, P R China. halmurat@263.net.

ABSTRACT

Background: Traditional Uighur medicine shares an origin with Greco-Arab medicine. It describes the health of a human body as the dynamic homeostasis of four normal Hilits (humours), known as Kan, Phlegm, Safra, and Savda. An abnormal change in one Hilit may cause imbalance among the Hilits, leading to the development of a syndrome. Abnormal Savda is a major syndrome of complex diseases that are associated with common biological changes during disease development. Here, we studied the protein expression profile common to tumour patients with Abnormal Savda to elucidate the biological basis of this syndrome and identify potential biomarkers associated with Abnormal Savda.

Methods: Patients with malignant tumours were classified by the diagnosis of Uighur medicine into two groups: Abnormal Savda type tumour (ASt) and non-Abnormal Savda type tumour (nASt), which includes other syndromes. The profile of proteins that were differentially expressed in ASt compared with nASt and normal controls (NC) was analysed by iTRAQ proteomics and evaluated by bioinformatics using MetaCore™ software and an online database. The expression of candidate proteins was verified in all plasma samples by enzyme-linked immunosorbent assay (ELISA).

Results: We identified 31 plasma proteins that were differentially expressed in ASt compared with nASt, of which only 10 showed quantitatively different expression between ASt and NC. Bioinformatics analysis indicated that most of these proteins are known biomarkers for neoplasms of the stomach, breast, and lung. ELISA detection showed significant upregulation of plasma SAA1 and SPP24 and downregulation of PIGR and FASN in ASt compared with nASt and NC (p < 0.05).

Conclusions: Abnormal Savda may be causally associated with changes in the whole regulation network of protein expression during carcinogenesis. The expression of potential biomarkers might be used to distinguish Abnormal Savda from other syndromes.

Show MeSH
Related in: MedlinePlus