Haptoglobin polymorphisms and fucosylation change: possible influence of variation on the identified lung cancer-relevant biomarkers

2020 ◽  
Vol 17 ◽  
Author(s):  
Kongsak Boonyapranai ◽  
Sakaewan Ounjaijean ◽  
Kanokwan Kulprachakarn ◽  
Laddawan Potpromanee ◽  
Miles Chih-Ming Chen ◽  
...  

Background: Haptoglobin (Hp), an acute-phase protein, is known as a potential diagnostic biomarker in human diseases. Two alleles of Hp (Hp1 and Hp2) exist in humans allowing three phenotypes (Hp1-1, Hp2-1, and Hp2-2), which influence the biophysical and biological properties of Hp. Objective: This work aimed to investigate the variation of serum level and fucosylation change among Hp phenotypes in pa-tients with lung cancer compared to healthy donors. Method: 44 patients with lung cancer and 26 healthy blood donors who lived in the Northern-Thailand region were investi-gated by glycoproteomic procedure. Results: The phenotypic distribution of the Hp (Hp1-1:Hp2-1:Hp2-2) in healthy donors were 0.04:0.38:0.58, while the pa-tient group were 0.09:0.52:0.39. The Hp1 allele frequency of the patients with lung cancer (0.34) was higher than the healthy donor (0.23). Glycoprotein blotting technique represented that the level of serum Hp and its fucosylation were sig-nificantly higher among lung cancer patients compared to those of the healthy donors. However, a downward trend in the fucosylation level from Hp1-1 to Hp2-1, Hp2-2, was seen in the patient group, but varying in the serum Hp level. An N-linked glycan was enzymatically released from discrete Hp multimers of Hp2-1 and Hp2-2 samples. Analysis of glycan pro-filing by MALDI-TOF-MS showed that reduction of the fucosylated glycan was associated with the size of Hp multimers, resulting in the lower level of fucosylation in Hp2-1 and Hp2-2, respectively. Conclusion: Our finding demonstrates that the Hp phenotype is a dependent risk factor for lung cancer and should be incor-porated into further clinical and biochemical investigations of diseases, including lung cancer.

2009 ◽  
Vol 205 (9) ◽  
pp. 639-647 ◽  
Author(s):  
Mahdi Abdullah ◽  
Holger Schultz ◽  
Daniel Kähler ◽  
Detlev Branscheid ◽  
Klaus Dalhoff ◽  
...  

2021 ◽  
Author(s):  
Nan Wang ◽  
Li Zhang ◽  
Qi Ying ◽  
Zhentao Song ◽  
Aiping Lu ◽  
...  

Abstract Background: Systematic quantification of phosphoprotein within cell signaling networks in solid tissues remains challenging and precise quantification in large scale samples has great potential for biomarker identification and validation. Methods:We developed a reverse phase protein array (RPPA) based phosphor-antibody characterization workflow by taking advantage of the lysis buffer compatible with alkaline phosphatase (AP) treatment and here termed it as a bottom-up antibody screening that differs from the conventional RPPA antibody validation procedure and applied it onto fresh frozen and formalin-fixed and paraffin-embedded tissue (FFPE) to test its applicability.Results:We tested the feasibility of this method by screening 106 phospho-antibodies with RPPA first followed by western blots on a panel of cell lines and demonstrated that AP treatment could serve as an independent factor that can be adopted for rapid RPPA phospho-antibody selection. We also performed studies on different clinical materials. For fresh frozen (FF) samples, pre-selected highly-specific antibodies showed a desirable data reproducibility and antibody specificity based on AP treatment indicating a potential for fresh tissue-based phospho-protein RPPA profiling. Of further clinical significance, using the same approach, based on two sets of FFPE samples from 63 melanoma and 40 lung cancer patients, we showed great interexperimental reproducibility and significant correlation with pathological markers MelanA for melanoma as well as a panel of lung cancer biomarkers for subtyping (EGFR, Napsin A, p63/p40, TTF1 and CK7) generating meaningful data that match clinical features. Conclusions:Our findings establish a highly efficient approach for phospho-antibody characterization by taking advantage of RPPA whereby the same methodology can be applied for tissue-based proteomics and phosphoproteomics in clinical assay development and application.


2016 ◽  
Vol 4 (2) ◽  
pp. 162-166 ◽  
Author(s):  
N. Khranovska ◽  
O. Skachkova ◽  
V. Sovenko ◽  
P. Sydor ◽  
M. Inomistova ◽  
...  

This study aimed to investigate phenotypical and functional characteristics of dendritic cells (DCs) generated from monocytes of peripheral blood of healthy donors and cancer patients.Material and methods. DCs were used as natural adjuvants with antitumor vaccine as a part of combined treatment scheme for lung cancer patients. Phenotypical and functional characteristics of DCs were study using flow cytometry and real-time PCR.Results. We have found that in lung cancer patients generated DCs had moderate level of maturity and demonstrated more pronounced tolerogenic features in contrast to DCs of healthy donors (patients DCs had higher mRNA expression levels of suppressive molecules TGF-β and IDO, and secreted lower amount of bioactive IL-12 protein). Expression of CCR7 gene was particularly on the normal level in DCs of cancer patients which indicates on saving of migratory properties of these cells. Expression level of DC maturity marker CD83 increased after each subsequent vaccine administration, while the levels of TGF-β, IL-10 mRNAs to the end of vaccine therapy course decreased to the level observed in healthy donors DCs.Conclusion. Thus, the study of biological characteristics of DCs will help to improve and develop the most effective protocols for rational use of DC vaccines. These data indicate the need for further optimization of technologies of DC generation in patients with lung cancer with emphasis on the stimulation of Th1-polarizing properties by increasing cytokine-secreting potential.


Author(s):  
Р.А. Титов ◽  
В.И. Минина ◽  
М.Л. Баканова ◽  
Я.А. Савченко

Обследовано 540 жительниц Кемеровской области: 270 человек, первично обратившиеся для диагностики и лечения в Кемеровский областной онкологический диспансер и 268 человек - здоровые женщины доноры Кемеровского областного центра крови (группа сравнения). Цель: изучение роли полиморфизма генов репарации ДНК в формировании рака легкого у женщин. Типирование полиморфных вариантов генов APEX1 (rs1130409), XRCC1 (rs25489), hOGG1 (rs1052133), XPD (rs13181), XPG (rs17655), XPC (rs2228001), ADPRT (rs1136410), АТМ (rs18015), NBS1 (rs1805794) осуществляли методом аллель-специфической ПЦР. Стaтистическую обрaботку результатов проводили с использованием программ: SNPstats (http://bioinfo.iconcologia.net/SNPstats), «Statistica 10.0» (StatSoft, Inc., USA). Выявлены ассоциации полиморфных вариантов генов APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489), АТМ (rs18015), XPC (rs2228001) c формированием рака легкого у женщин. In the presented «case-control» study 540 residents of the Kemerovo Region subject to age, sex and smoking status were included. We formed two groups: 1) «Case» - 270 newly diagnosed lung cancer patients undergoing a medical treatment in the Kemerovo Regional Oncology Center; 2) «Control» - 268 healthy donors of the Kemerovo Regional Center of Blood Transfusion. Statistical analysis were performed using SNPstats (http://bioinfo.iconcologia.net/SNPstats), «Statistica 10.0» (StatSoft, Inc., USA). A significant association obtained between the APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489), АТМ (rs18015), XPC (rs2228001)) and lung cancer.


2021 ◽  
Author(s):  
Kangyu Wang ◽  
Xingguo Song ◽  
Xinyi Li ◽  
Zhijun Zhang ◽  
Li Xie ◽  
...  

Aim: This study aimed to access the efficacy of plasma small nucleolar RNAs in early diagnosis of non-small-cell lung cancer (NSCLC). Methods: SNORD83A was selected based on databases and further verified in 48 paired formalin-fixed, paraffin-embedded tissues, as well as in plasma from 150 NSCLC patients and 150 healthy donors. The diagnostic efficiency of plasma SNORD83A, as well as in combination with carcinoembryonic antigen, was determined by receiver operating characteristic analysis. Results: SNORD83A was significantly increased not only in tissues but also in plasma from NSCLC patients compared with those from healthy donors. Plasma SNORD83A was able to act as a diagnostic biomarker for NSCLC. The diagnostic efficiency of carcinoembryonic antigen was also significantly elevated for early-stage NSCLC when combined with SNORD83A. Conclusion: SNORD83A can serve as a diagnostic biomarker for NSCLC.


1983 ◽  
Vol 61 (4) ◽  
pp. 376-380 ◽  
Author(s):  
R. Bell ◽  
L. Hoffman-Goetz

Endogenous pyrogen (EP) is known to trigger a rise in the plasma concentrations of various acute phase reactant proteins. This study describes the effects of chronic protein deficiency in rabbits on EP-mediated changes in the plasma concentrations of fibrinogen, albumin, and α2-macroglobulm. Injection (i.v.) of EP from healthy donors into protein-deprived rabbits produced a smaller rise in plasma fibrinogen and α2-maeroglobulin, and a smaller fall in plasma albumin than injection of EP into controls. Injection of EP, obtained from malnourished donors, into healthy rabbits also resulted in an attenuation of the acute phase protein response. These data are consistent with the hypothesis that EP activity is influenced by the nutritional status of both the donor and recipient of EP.


2021 ◽  
Vol 32 ◽  
pp. S300
Author(s):  
Yasushi Yatabe ◽  
Makoto Nishio ◽  
Toshiaki Takahashi ◽  
Kazumi Nishino ◽  
Yasumasa Yoshiki ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21014-21014
Author(s):  
L. Chen ◽  
Y. Wang ◽  
Z. Yu

21014 Objective: To detect the hypermethylation status of RASSF1A promoter in serum DNA of lung cancer patients and to analyze its correlation with clinicopathological features. Methods: Serum DNA was extracted from peripheral blood from 80 primary lung cancer patients, 35 benign pulmonary disease patients and 15 healthy donors. The methylation status of RASSF1A promoter was determined using methylation-specific PCR technique, and the correlation between methylation profiles and clinicopathological parameters was statistically analyzed. Results: Aberrant methylation of RASSF1A was detected in 27 of the 80 (33.8%) patients with lung cancer but no benign pulmonary disease patients or healthy donors (p<0.001). RASSF1A was preferentially observed in small cell lung cancer (p=0.042), while no statistical difference was found among methylation frequencies of different subtypes of non-small cell lung cancer. The methylation status was also found to be associated with relative poor differentiation (p=0.009) and late stage (p=0.013), but not with gender, age or treatment. Conclusion: RASSF1A promoter is frequently hypermethylated in serum DNA of primary lung cancer patients, and RASSF1A is a promising novel biomarker for lung cancer diagnosis. No significant financial relationships to disclose.


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