Razi Journal of Medical Sciences

fa میزان سطح RNA سرمی ژن 2 Stanniocalcin در بیماران مبتلا به سرطان معده Serum RNA level of Stanniocalcin-2 gene in patients with gastric cancer ژنتیک Genetic پژوهشي Research زمینه و هدف: <a name="_Hlk528450380">سرطان به ترتیب در کشورهای توسعه یافته و درحال توسعه اولین و دومین عامل مرگ می‌باشد. </a>روش‌های تهاجمی میکروسکوپی و اندوسکوپی بطور روتین برای غربالگری سرطان معده مناسب نمی باشد، بنابراین نیاز به بیومارکرهایی با توانایی تشخیص سریع، ساده و با حساسیت بالا در مراحل اولیه سرطان ، به شدت احساس می‌شود. هورمون استانیوکلسین در تنظیم کلسیم و فسفر بدن نقش داشته و علاوه بر آن در تمایز سلول های نورون، رگزایی، ترمیم زخم ها، باروری و تکامل جنین و سرطان نیز نقش دارد. ‌این مطالعه با هدف بررسی میزان بیان ژن استانیوکلسین 2 ( STC2) در سرم بیماران مبتلا به سرطان معده انجام گرفت. روش کار: ‌این مطالعه مورد شاهدی بر روی نمونه‌های مربوط به 50 بیمار مبتلا به سرطان معده (مورد) و 50 فرد سالم (کنترل) انجام گرفت. نمونه خون محیطی از بیماران مبتلا به سرطان معده و نیز افراد داوطلب به عنوان گروه کنترل در لوله‌های حاوی ماده ضد انعقادی EDTA جمع‌آوری و بلافاصله تحت جداسازی سرم قرار گرفتند. پس از طی مراحل سانتریفوژ RNA  سرمی استخراج و بعد از سنتز cDNA، با روش Taq Man  وReal- time PCR  و با استفاده از پرایمرها و پروب‌های اختصاصی، سطح RNA سرمی ژن STC2 اندازه گیری گردید. سپس نتایج ارزیابی‌های سرمی و اطلاعات کلینیکوپاتولوژیکی بیماران و گروه کنترل بهمراه اطلاعات حاصل از بررسی پرونده‌های بیماران و یافته‌های دموگرافیک و جداول تنظیمی و نمودارهای مربوطه جمع آوری شد. برای آنالیز اطلاعات توصیفی از نرم ‌افزار SPSS22 استفاده شد. یافته‌ها: طبق نتایج حاصل از مطالعه، بیان بالای ژن STC2 در گروه مورد 26 مورد (52 درصد) و در گروه کنترل 8 مورد (16 درصد) بود. اگرچه ارتباط معنی داری بین بیان بالای ژن STC2 و ابتلا به سرطان گاستریک وجود داشت (0001/0p= ) اما ارتباط معنی داری بین جنسیت بیماران و بیان بالای ژن STC2 وجود نداشت (73/0 = P).  با این وجود سن 32 درصد بیماران بیشتر از 65 سال بود و ارتباط معنی داری بین سن بیماران و بیان بالای ژن STC2 وجود داشت (031/0 = P). اگرچه ارتباط معنی داری بین محل آناتومیک سرطان و نیز ساب تایپ‌های سرطان و بیان بالای ژن STC2 وجود نداشت اما بین میزان تمایز یافتن سرطان و بیان بالای ژن  STC2 ارتباط معنی داری وجود داشت (05/0 P ≤). نتیجه‌گیری:  STC2 می تواند به عنوان بیومارکر جهت تعیین مرز و حاشیه های تومور مورد استفاده قرار گیرد. آنالیز بیان ژن STC2 در طول عمل جراحی می تواند در کاهش خطای جراحی در برداشتن تومور و افزایش موفقیت جراحی برای پاکسازی تومور مورد استفاده قرار گیرد. <div style="text-align: justify;">Background & Aims: Cancer is the leading cause of death in developed and developing countries, respectively. Microscopic and endoscopic invasive procedures are not routinely suitable for screening gastric cancer, so the need for biomarkers with the ability to detect quickly, easily, and with high sensitivity in the early stages of cancer is strongly felt. This study aimed to evaluate the expression of the Stanniocalcin 2 (STC2) gene in the serum of patients with gastric cancer. Although the incidence of gastric cancer in the world, especially in developed countries such as the United States has decreased in recent decades (1), in Iran the incidence is increasing and this increase is particularly significant in western Iran (2). According to the latest research conducted in 1988 in Iran, the rate of gastric cancer is 9.3 percent and the third most common cancer in the country in the total number of women and men (2). According to research, Ardabil province has the highest incidence of cancer in Iran and the highest incidence of gastric cancer (49.1 cases per 100,000 in men and 25.4 cases per 100,000 in women), which is almost seven times higher than in southern parts of Iran and twice Is higher than the global average (3). Gastric cancer is a multifactorial disease and has a multi-stage process, including cancer-causing factors that can be attributed to multiple infectious, environmental, genetic, and epigenetic factors on genes that suppress and repair tumors, nutrition, lifestyle, age, and race Pointed out (4). In more than half of the advanced cases in people with this disease, no symptoms are observed and it is diagnosed when it has entered the advanced stage, and unfortunately, many of these people die after a short time. The fast and timely disease can increase the 5-year survival rate of infected people up to 60% (5). Methods: Peripheral blood samples were collected from patients with primary gastric cancer as well as volunteers in tubes containing EDTA anticoagulants. Samples were immediately isolated from serum. Total RNA was extracted from the serum of control and patient samples. The cDNA was then synthesized using the Omniscript Reverse Transcriptase enzyme produced by the German company Qiagen and from a pattern string. The concentration and quality of RNA extracted were measured by adsorption intensity (OD) readings by a spectrophotometer (Nanodrop). SPSS 22 software was used for data analysis and due to the lack of normal distribution of data, Spearman correlation coefficient and Mann-Whitney U test and Kruskal-Wallis tests were used for analysis. Levels less than 0.05 were considered significant. Results: There was no significant relationship between patients' sex and high expression of the STC2 gene (P = 0.73). The age of 32% of patients was more than 65 years. There was a significant relationship between patients' age and high expression of the STC2 gene (P = 0.031). Most tissue samples were moderate in differentiating cancer (21 cases, 42%). There was no significant relationship between cancer differentiation and high expression of the STC2 gene (P = 0.34). Most patients (18 patients, 36% of them) were in the T3 stage. There was a significant relationship between TNM classification of cancer and high expression of the STC2 gene (P = 0.001). A study entitled clinical significance of stanniocalcin2 expression as a predictor of tumor progression in gastric cancer was conducted in 2013 by Origami et al. In this study, a quantitative PCR test was used to evaluate the expression of STC2 mRNA in 4 gastric cancer cells and the blood samples of 93 patients with gastric cancer and 22 healthy volunteers. They concluded that the number of STC2 mRNA transcripts in gastric cancer cells and the blood of patients with gastric cancer was higher than that of healthy volunteer blood (P = 0.0002 and P = 0.01). STC2 gene expression was positive in 43 patients (46.2%) out of 93 patients with gastric cancer and its expression was significantly related to age, depth of tumor attack, lymph node metastasis, stage invasion and venous (P = 0.023, P = 0.045, P = 0.035, P = 0.007 and P = 0.027). The 5-year survival rate in patients with STC2 expression was significantly lower compared to patients without STC2 expression (P = 0.014). Our results suggest that STC2 by monitoring CTC in patients with gastric cancer can be a useful molecular blood marker for predicting tumor progression (17). The above study is also in line with our study. A study entitled clinical-pathological significance of stanniocalcin2 gene expression in colorectal cancer was conducted in 2017 by Ita et al. In this study, the expression of STC2 and clinical pathology were examined in 139 colorectal cancer specimens using PCR. They concluded that STC2 was more pronounced in colorectal cancer cells than in normal colorectal epithelial cells. The most common anatomical site was gastric trunk cancer and intestinal subtype was seen in most cases. Increased expression of STC2 was observed in 26 patients with gastric cancer (52%) and the control group 8 cases (16%). There was a significant association between high STC2 gene expression and gastric cancer. The present study failed to show a relationship between age, sex, tumor differentiation, anatomical location of gastric cancer, cancer subtypes, and increased STC2 expression. But it showed that there was a significant relationship between the frequency of cases with increased STC2 expression and age over 65 years and TNM classification of cancer. Conclusion: Our results showed that STC2 in patients with gastric cancer could be a useful molecular blood marker for predicting tumor progression.  </div> سرطان معده, ژن استانیوکلسین 2,RNA سرمی,Real-time PCR,بیومارکر Gastric cancer, Stanniocalcin2 gene, Serum RNA, Real time PCR, Biomarker 196 203 http://rjms.iums.ac.ir/browse.php?a_code=A-10-6207-1&slc_lang=fa&sid=1 Saeed Hosseini Asl سید سعید حسینی اصل Hosseini.original@yahoo.com 3900319475328460090452 3900319475328460090452 No Assistant Professor, Department of Genetics and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran استادیار، گروه ژنتیک و پاتولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی و خدمات بهداشتی درمانی اردبیل، اردبیل، ایران Iraj Feizi ایرج فیضی feizi.iraj@gmail.com 3900319475328460090453 3900319475328460090453 No Associate Professor, Department of Surgery, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran دانشیار، گروه جراحی، دانشکده پزشکی، دانشگاه علوم پزشکی و خدمات بهداشتی درمانی اردبیل، اردبیل، ایران Alireza Abhari علیرضا ابهری abharial@tbzmed.ac.ir 3900319475328460090454 3900319475328460090454 No Assistant Professor, Department of Laboratory sciences, Sarab Faculty of Medical Sciences, Sarab, Iran استادیار، گروه علوم آزمایشگاهی، دانشکده علوم پزشکی سراب، سراب، ایران Amir Ahmad Arabzadeh امیراحمد عرب زاده amir_medico@Yahoo.com 3900319475328460090455 3900319475328460090455 Yes Assistant Professor, Department of Surgery, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran استادیار، گروه جراحی، دانشکده پزشکی، دانشگاه علوم پزشکی و خدمات بهداشتی درمانی اردبیل، اردبیل، ایران