CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER

Serkan Göktuna

doi:10.23902/trkjnat.1139062

Research Article

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CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER

Year 2022, , 177 - 184, 15.10.2022

Serkan Göktuna

https://doi.org/10.23902/trkjnat.1139062

Abstract

The aim of this study is to characterize tumor cell specific expression of purinergic ecto-enzymes CD39 and CD73, and to associate prognostic significance of these expression patterns in colorectal cancer (CRC) patients. Protein and gene expression of the target genes in various CRC cell lines were assessed via Western Blot (WB) analysis and Real Time PCR (RT-PCR). Additionally, tumor vs stromal cell expression of the target genes was analyzed from publicly available patient expression datasets. Finally, the correlation between CD39 and CD73 expression with patient prognosis was analyzed via The Cancer Genome Atlas (TCGA) datasets. In CRC cell lines, CD39 was found to be not expressed at all while CD73 was expressed extensively in most cell lines via WB and RT-PCR analyses. Patient microarray expression data confirmed the results from CRC cell lines that CD39 expression was very low in epithelial/tumor cells relative to other stromal cell types yet CD73 was expressed abundantly in every cell type within patient tumor samples. Interestingly, CD39 expression in patient tumors was correlated with favorable prognosis while CD73 expression was associated with worse prognosis. Although CD39 and CD73 are related enzymes involved in extracellular purinergic signaling, their expression patterns in tumor cells and prognostic effects in patients show opposing outcomes. Therefore, better insights in understanding the functional involvement of purinergic ecto-enzymes in colorectal tumor development is needed via further mechanistic studies.

Keywords

Cancer, Adenosine, CD39, CD73, prognosis

Supporting Institution

TÜBİTAK

Project Number

118S399

Thanks

I thank to Dr. Seçil Demirkol Canlı (Hacettepe University, Ankara) for assistance in bioinformatic analysis of human tumor samples for CD39 and CD73 expression; Prof. Sreeparna Banerjee (METU, Ankara) for providing Caco-2 cells; Prof. İhsan Gürsel (iBG, İzmir) for providing unstimulated Jurkat and Namalwa cell lysates or mRNA; Prof. Florian Greten (GSH and FCI, Frankfurt) for providing HT-29 cells; and Dr. Tieu Lan Chau (Bilkent University, Ankara) for technical assistance for in vitro gene expression analyses.

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Year 2022, , 177 - 184, 15.10.2022

Serkan Göktuna

https://doi.org/10.23902/trkjnat.1139062

Abstract

Bu çalışmanın amacı pürinerjik ekto-enzimler CD39 ve CD73'ün tümör hücresine özgü ifadesini karakterize etmek ve kolorektal kanser (KRK) hastalarında bu ifade örgülerinin prognostik öneminin anlaşılmasıdır. Çeşitli KRK hücre hatlarında hedef genlerin protein ve gen ifadesi, Western Blot (WB) ve Real Time PCR(RT-PCR) yoluyla değerlendirildi. Bunun yanında hedef genlerin tümör ve stromal hücrelerdeki ifadesi kamuya açık hasta ifade veri setleri vasıtasıyla analiz edildi. Son olarak, CD39 ve CD73 ifadesi ile hasta prognozu arasındaki ilişki The Cancer Genome Atlas (TCGA) veri setleri aracılığıyla analiz edildi. KRK hücre hatlarında CD39'un hiç ifade edilmediği, CD73'ün ise çoğu hücre hattında yoğun şekilde ifade edildiği WB ve RT-PCR analizleri yoluyla bulundu. Hasta mikrodizin ifade verileri, CD39 ifadesinin epitelyal/tümör hücrelerinde diğer stromal hücre tiplerine göre çok düşük olduğunu, ancak CD73'ün hasta tümör örneklerindeki her hücre tipinde bol miktarda ifade edildiğini KRK hücre hatlarından elde edilen sonuçları doğrular biçimde ortaya konuldu. İlginç bir şekilde, hasta tümörlerinde CD39 ifadesi iyi prognoz ile ilişkili olarak bulunurken CD73 ifadesi ise kötü prognoz ile ilişkili olarak gözlenmiştir. CD39 ve CD73 hücre dışı pürinerjik sinyal yolağında yer alan ilgili enzimler olmalarına rağmen tümör hücrelerindeki ifade örgüleri ve hasta prognozlarındaki etkilerinde birbirine zıt sonuçlara ulaşılmıştır. Sonuç olarak kolorektal tümör gelişiminde pürinerjik ekto-enzimlerin fonksiyonel katılımını daha iyi anlamak için daha ileri mekanistik çalışmalara ihtiyaç vardır.

Project Number

118S399

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Details

Primary Language	English
Subjects	Structural Biology
Journal Section	Research Article/Araştırma Makalesi
Authors	Serkan Göktuna 0000-0001-6169-768X
Project Number	118S399
Publication Date	October 15, 2022
Submission Date	July 6, 2022
Acceptance Date	September 6, 2022
Published in Issue	Year 2022

Cite

APA	Göktuna, S. (2022). CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER. Trakya University Journal of Natural Sciences, 23(2), 177-184. https://doi.org/10.23902/trkjnat.1139062
AMA	Göktuna S. CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER. Trakya Univ J Nat Sci. October 2022;23(2):177-184. doi:10.23902/trkjnat.1139062
Chicago	Göktuna, Serkan. “CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER”. Trakya University Journal of Natural Sciences 23, no. 2 (October 2022): 177-84. https://doi.org/10.23902/trkjnat.1139062.
EndNote	Göktuna S (October 1, 2022) CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER. Trakya University Journal of Natural Sciences 23 2 177–184.
IEEE	S. Göktuna, “CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER”, Trakya Univ J Nat Sci, vol. 23, no. 2, pp. 177–184, 2022, doi: 10.23902/trkjnat.1139062.
ISNAD	Göktuna, Serkan. “CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER”. Trakya University Journal of Natural Sciences 23/2 (October 2022), 177-184. https://doi.org/10.23902/trkjnat.1139062.
JAMA	Göktuna S. CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER. Trakya Univ J Nat Sci. 2022;23:177–184.
MLA	Göktuna, Serkan. “CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER”. Trakya University Journal of Natural Sciences, vol. 23, no. 2, 2022, pp. 177-84, doi:10.23902/trkjnat.1139062.
Vancouver	Göktuna S. CHARACTERIZATION OF DIFFERENTIAL EXPRESSION PATTERNS OF THE EXTRACELLULAR PURINERGIC ENZYMES IN COLORECTAL CANCER. Trakya Univ J Nat Sci. 2022;23(2):177-84.

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