New Cellularand Molecular Biotechnology Journal
مجله تازه هاي بيوتكنولوژي سلولي و مولكولي
NCMBJ
Basic Sciences
http://ncmbjpiau.ir
1
admin
2228-5458
2228-6926
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8888
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fa
jalali
1404
1
1
gregorian
2025
4
1
15
58
online
1
fulltext
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بررسی ارتباط بالینی واریانتهای ناحیۀ 5′ UTR ژن TYMS در پاسخ به شیمیدرمانی بیماران سرطان معده در ایران
Investigating the clinical relevance of variants in the 5′ UTR region of the TYMS gene in response to chemotherapy in Iranian gastric cancer patients
سلولی و مولکولی
Cellular and molecular
مقاله پژوهشی
Research Article
<span style="font-size:10pt"><span style="background:white"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Book Antiqua",serif"><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">سابقه</span></span></span></b><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> و هدف:</span></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> واریانتهای </span></span></span><b><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژنتیکی مارکرهای ارزشمندی برای پیشبینی مقاومت به شیمیدرمانی هستند. <i>تیمیدیلات</i> <i>سنتتاز</i> (</span></span></span><i><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">) هدف آنزیمی مهمی در بیماران سرطان معده درمان</span></span></span><b><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">شده با شیمی</span></span></span><b><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">درمانی نئوادجوانت بر پایه 5- فلورویوراسیل است. واریانتهای ژنتیکیِ ژن <i>تیمیدیلات</i> <i>سنتتاز</i> بر بیان</span></span></span><b><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژن و مقاومت به شیمی</span></span></span><b><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">درمانی در بیماران سرطان معده مؤثر</span></span></span><b><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> است. هدف این مطالعه بررسی واریانتهای </span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژن</span></span></span><b> </b><i><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></i><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> و امکان تأثیر آللهای آنها بر مقاومت دارویی، بقا و بیان</span></span></span><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژن در بیماران سرطان معده</span></span></span><span dir="LTR" style="font-family:"Times New Roman",serif"><span style="color:black"></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> است.</span></span></span><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""></span></span></b></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="background:white"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">مواد و روش</span></span></span></b><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ها</span></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">: آنالیز ژنتیکی روی بخشهای نرمال بلوکهای پارافینۀ 100 بیمار سرطان معده انجام شد. تمام بیماران شیمی</span></span></span><b><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">درمانی نئوادجوانت بر پایۀ 5- فلورویوراسیل را دریافت کرده بودند. ژنوتیپ واریانت</span></span></span><b><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">های </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">rs34743033</span></span></span><b><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> (</span></span></span></b><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><b> </b><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">28</span></span></span><b> </b><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">bp</span></span></span><b> </b><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">VNTR</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">) و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">rs2853542</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> (</span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"> SNP C>G</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">) به</span></span></span><b><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">روش </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">PCR</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> و</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">PCR</span></span></span><b> </b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">-</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">RFLP</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> تعیین و بیان</span></span></span><b><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژن در بافت تومور و حاشیه تومور بیماران بررسی شد. </span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""></span></span></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="background:white"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">یافته ­ها: </span></span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ارتباط معناداری بین ژنوتیپهای </span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"> 28 bp VNTR</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> و درمان مشاهده شد (003/0=</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">P</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">). بیماران با ژنوتیپ </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">2R3R</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> پاسخ بهتری به درمان نشان دادند. بیشترین و کمترین زمان بقا بهترتیب ژنوتیپهای </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">3R3R3</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> و </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">2R2R</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> بود (003/0=</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">P</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">). بین بیان</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژن و واریانتهای </span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"> 28 bp VNTR</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> <i>و<a name="_Hlk147858579"> </a></i></span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"> SNP C>G</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> ارتباط معناداری وجود داشت (001/0></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">P</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">). ژنوتیپ </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">CC</span></span></span><span style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> واریانت </span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black"> SNP C>G</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> با بیانِ کمتر و ژنوتیپ </span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">CG</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> با بیان بیشتر ژن مرتبط بود.</span></span></span><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""></span></span></b></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="background:white"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">نتیجه</span></span></span></b><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span><b><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">گیری:</span></span></span></b> <span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">این مطالعه نشان داد که تعیین ژنوتیپها و بیان</span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="color:black"></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black">ژن </span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"><span style="color:black">TYMS</span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""><span style="color:black"> میتواند برای پیشبینی بقای بیماران مبتلا به سرطان معده و پاسخ به شیمیدرمانی بر پایۀ 5- فلورویوراسیل مؤثر باشد.</span></span></span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Nazanin""></span></span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:10.0pt">Aim and Background</span></b><b><span style="font-size:10.0pt"><span style="letter-spacing:-.1pt">:</span></span></b><span style="font-size:10.0pt"> Genetic variants are valuable markers for predicting chemotherapy resistance. Thymidylate synthetase is an important enzyme target in gastric cancer patients treated with neoadjuvant 5-fluorouracil-based chemotherapy. Genetic variants in the thymidylate synthetase gene are effective in gene expression and resistance to chemotherapy in gastric cancer patients. Therefore, the aim of this study is to investigate the variants of the <i>TYMS</i> gene and the possible effect of their alleles on drug resistance, survival, and gene expression in gastric cancer patients.<span style="background:fuchsia"></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:10.0pt"><span style="background:white"><span style="color:black">Materials and Methods</span></span></span></b><b><span style="font-size:10.0pt">:</span></b><span style="font-size:10.0pt"> Genetic analysis was performed on normal sections of paraffin blocks of 100 patients. All patients received neoadjuvant chemotherapy based on 5-fluorouracil. The genotypes of rs34743033 (<i>TYMS</i> 28-bp VNTR) and rs2853542 (<i>TYMS</i> SNP C>G) variants were determined, and gene expression was investigated in tumor tissue and tumor margins of patients<span style="background:fuchsia"></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="background:white"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman",serif"><b><span style="font-size:10.0pt"><span style="color:black">Results:</span></span></b><span style="font-size:10.0pt"><span style="color:black"> A significant association between <i>TYMS</i> 28</span></span> <span style="font-size:10.0pt"><span style="color:black">bp VNTR genotypes and treatment was observed (P=0.003). Patients with the 2R3R genotype showed a better response to treatment. The highest and lowest survival times were observed for the 3R3R and 2R2R genotypes, respectively (P=0.003). There was a significant relationship between gene expression and the <i>TYMS</i> 28 bp VNTR variant and the <i>TYMS</i> SNP C>G variant (P<0.001). The CC genotype of the <i>TYMS</i> SNP C>G variant was associated with lower gene expression and the CG genotype was associated with higher gene expression.</span></span><span style="font-size:10.0pt"><span style="background:fuchsia"></span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif">Conclusion:</span></span></b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"> This study showed that determining the genotypes and expression of the <i>TYMS</i> gene can be effective for predicting the survival of gastric cancer patients and their response to 5-fluorouracil-based chemotherapy.</span></span></span></span></span></span></span><br>
مقاومت به شیمی درمانی, سرطان معده, پزشکی شخصی, TYMS
Chemoresistance, Gastric cancer, Personalized medicine, TYMS.
81
93
http://ncmbjpiau.ir/browse.php?a_code=A-10-1970-2&slc_lang=other&sid=1
khadijeh
Arjmandi
خدیجه
ارجمندی
100319475328460015351
100319475328460015351
No
Tehran Azad University, Science and Research Branch
گروه زیستشناسی، واحد علوم و تحقیقات تهران، دانشگاه آزاد اسلامی، تهران، ایران.
Iman
Salahshouri
ایمان
سلحشوری فر
isalahshouri@gmail.com
100319475328460015352
100319475328460015352
Yes
Department of Biology, SR.C.,Islamic Azad University , Tehran , Iran
گروه زیستشناسی، واحد علوم و تحقیقات تهران، دانشگاه آزاد اسلامی، تهران، ایران
Fereshteh
Ameli
فرشته
عاملی
100319475328460015353
100319475328460015353
No
Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
گروه پاتولوژی ، انستیتو کانسر مجتمع بیمارستان امام خمینی ، دانشگاه علوم پزشکی تهران ، تهران ، ایران
shiva
Irani
شیوا
ایرانی
100319475328460015354
100319475328460015354
No
Tehran Azad University, Science and Research Branch
دانشگاه آزاد واحد علوم تحقیقات تهران
Ohsen
Esfandbod
محسن
اسفندبد
100319475328460015355
100319475328460015355
No
Department of Hematology and Oncology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
بخش هماتولوژی و آنکولوژی ، مجتمع بیمارستان امام خمینی، دانشگاه علوم پزشکی تهران، تهران، ایران