International Journal of Reproductive BioMedicine
International Journal of Reproductive BioMedicine
IJRM
Medical Sciences
http://ijrm.ir
1
admin
2476-4108
2476-3772
10.29252/ijrm
en
jalali
1402
7
1
gregorian
2023
10
1
21
10
online
1
fulltext
en
شناسایی ژن های هاب داروپذیر و مسیرهای کلیدی مرتبط با سرطان دهانه رحم با تجزیه و تحلیل برهمکنش پروتئین پروتئین: یک مطالعه in silico
Identification of druggable hub genes and key pathways associated with cervical cancer by protein-protein interaction analysis: An in silico study
Reproductive Oncology
Original Article
Original Article
<div style="text-align: justify;"><span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مقدمه: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">رشد کنترل نشده سلول­های غیرطبیعی در دهانه رحم منجر به شروع سرطان دهانه رحم، چهارمین سرطان شایع زنان می­شود. تاکنون مطالعات زیادی بر روی سرطان دهانه رحم انجام شده است، با این حال، کشف ژن­های هاب، مسیرهای کلیدی و مکانیسم­های دقیق ایجاد این بیماری ضروری به نظر می­رسد.</span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">هدف: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">هدف از این مطالعه استفاده از الگوهای بیان ژن و آنالیز شبکه برهمکنش پروتئین-پروتئین (</span></span><span dir="LTR" style="font-size:10.0pt">PPI</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">) برای شناسایی مسیرهای کلیدی و ژنهای هاب داروپذیر در درمان سرطان دهانه رحم می­باشد.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مواد و روش­ ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در این آنالیز </span></span><span dir="LTR" style="font-size:10.0pt">in silico</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، دو مجموعه داده بیان ژن ریزآرایه </span></span><span dir="LTR" style="font-size:10.0pt">GSE63514</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">(104 نمونه سرطان و 24 نمونه طبیعی) و </span></span><span dir="LTR" style="font-size:10.0pt">GSE9750</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> (42</span></span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">نمونه سرطان و 24 نمونه طبیعی) از سایت (</span></span><span dir="LTR" style="font-size:10.0pt">GEO</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">) </span></span><span dir="LTR" style="font-size:10.0pt">Gene Expression Omnibus</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> برای شناسایی ژن­های مشترک با بیان متفاوت در آنها، استفاده شد. تجزیه و تحلیل مسیر </span></span><span dir="LTR" style="font-size:10.0pt">GO</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">و </span></span><span dir="LTR" style="font-size:10.0pt">KEGG</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> از طریق پایگاه داده </span></span><span dir="LTR" style="font-size:10.0pt">Enrichr</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> انجام شد. پایگاه داده12.0 </span></span><span dir="LTR" style="font-size:10.0pt">STRING</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> و پلاگین </span></span><span dir="LTR" style="font-size:10.0pt">cytoHubba</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> در نرم­افزار 3.9.1 </span></span><span dir="LTR" style="font-size:10.0pt">Cytoscape</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> برای ایجاد و تجزیه و تحلیل شبکه برهم­کنش </span></span><span dir="LTR" style="font-size:10.0pt">PPI</span><span style="font-size:11.0pt"><span style="font-family:"B Mitra""> به کار برده شد. در نهایت، ژن­های هاب داروپذیر غربال شد.</span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">نتایج: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">پس از غربالگری شبکه برهم­کنش </span></span><span dir="LTR" style="font-size:10.0pt">PPI</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> بر اساس </span></span><span dir="LTR" style="font-size:10.0pt">degree</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">توسط پلاگین </span></span><span dir="LTR" style="font-size:10.0pt">cytoHubba</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، 10 ژن به عنوان ژن­های هاب مرتبط با سرطان دهانه رحم شناسایی شدند که شامل </span></span><i><span dir="LTR" style="font-size:10.0pt">NCAPG</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">KIF11</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">TTK</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">PBK</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">MELK</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">ASPM</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">،</span></span><i><span dir="LTR" style="font-size:10.0pt">TPX2</span></i> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">BUB1</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">TOP2A</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> و </span></span><i><span dir="LTR" style="font-size:10.0pt">KIF2C</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> می­باشند. در میان این ژن­های هاب، 5 ژن (</span></span><i><span dir="LTR" style="font-size:10.0pt">KIF11</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">TTK</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">PBK</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><i><span dir="LTR" style="font-size:10.0pt">MELK</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> و </span></span><i><span dir="LTR" style="font-size:10.0pt">TOP2A</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">) داروپذیر هستند.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">نتیجه ­گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">این تحقیق چشم­اندازی جدید برای طراحی اهداف درمانی در بیماران مبتلا به سرطان دهانه رحم ارائه می­دهد. با این حال، این یافته­ها باید از طریق آزمایش­های بیشتر تأیید شود</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">.</span></span></span></span></span></span></span></div>
<div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:11pt"><span style="background:white"><span style="line-height:normal"><b><span style="font-size:12.0pt">Background:</span></b><span style="font-size:12.0pt"> The uncontrolled growth of abnormal cells in the cervix leads to cervical cancer (CC), the fourth most common gynecologic cancer.</span> <span style="font-size:12.0pt">So far, many studies have been conducted on CC; however, it is still necessary to discover the hub gene, key pathways, and the exact underlying mechanisms involved in developing this disease. </span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Objective: </span></b><span style="font-size:12.0pt">This study aims to use gene expression patterns and protein-protein interaction (PPI) network analysis to identify key pathways and druggable hub genes in CC.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Materials and Methods:</span></b> <span style="font-size:12.0pt">In this in silico analysis,</span><span lang="EN" style="font-size:12.0pt"> 2 microarray gene expression datasets; GSE63514 (104 cancer and 24 normal samples), and GSE9750 (42 cancer and 24 normal samples) were extracted </span><span style="font-size:12.0pt">from gene expression omnibus to identify common differentially expressed genes between them. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analysis were performed via</span><span style="font-size:12.0pt"> the </span><span style="font-size:12.0pt">Enrichr database.</span><span lang="EN" style="font-size:12.0pt"> STRING 12.0 database and CytoHubba plugin </span><span style="font-size:12.0pt">in</span><span lang="EN" style="font-size:12.0pt"> Cytoscape 3.9.1 software were implemented to create and analyze the PPI network</span><span style="font-size:12.0pt">.</span> <span style="font-size:12.0pt">Finally,</span> <span style="font-size:12.0pt">druggable hub genes were screened.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Results: </span></b><span style="font-size:12.0pt">Based on the degree method, 10 key genes were known as the hub genes after the screening of PPI networks by the CytoHubba plugin. <i>NCAPG</i>, <i>KIF11</i>, <i>TTK</i>, <i>PBK</i>, <i>MELK</i>, <i>ASPM</i>, <i>TPX2</i>, <i>BUB1</i>, <i>TOP2A</i>, and <i>KIF2C</i> are the key genes, of which 5 genes (<i>KIF11</i>, <i>TTK</i>, <i>PBK</i>, <i>MELK</i>, and <i>TOP2A</i>) were druggable.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Conclusion: </span></b><span style="font-size:12.0pt">This research provides a novel vision for designing therapeutic targets in patients with CC. However, these findings should be verified through additional experiments.</span></span></span></span></div>
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<span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span style="font-family:"Times New Roman","serif""></span></span></b></span></span></span>
برهمکنش های پروتئین, سرطان دهانه رحم, ژن های هاب, بیان ژن, DEGs.
Protein interactions, Cervical cancer, Hub genes, Gene expression, DEGs.
809
818
http://ijrm.ir/browse.php?a_code=A-10-2513-1&slc_lang=en&sid=1
Azizeh
Asadzadeh
az.asadzadeh@gmail.com