[논문]자궁경부암 조직에서 에스트로겐 수용체 알파 mRNA의 진단적 유용성

김지혁; 유광민; 김정호; 김서용; 박선영; 안성우; 이지영; 김성현; 박호현; 이동섭

doi:10.15324/kjcls.2018.50.4.449

자궁경부암 조직에서 에스트로겐 수용체 알파 mRNA의 진단적 유용성
Diagnostic Availability of Estrogen Receptor Alpha mRNA on Cervical Cancer Tissue 원문보기

Korean journal of clinical laboratory science : KJCLS = 대한임상검사과학회지, v.50 no.4, 2018년, pp.449 - 456

김지혁 (연세대학교 임상병리학과) , 유광민 (연세대학교 임상병리학과) , 김정호 (연세대학교 임상병리학과) , 김서용 (연세대학교 임상병리학과) , 박선영 (연세대학교 임상병리학과) , 안성우 (연세대학교 임상병리학과) , 이지영 (연세대학교 임상병리학과) , 김성현 (부산가톨릭대학교 임상병리학과) , 박호현 (목포과학대학교 임상병리과) , 이동섭 (혜전대학교 임상병리과)

초록
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자궁경부암은 세계적으로 여성에서 네번째로 많이 진단되는 암이다. 개발 지수가 낮은 개발도상국이나 후진국에서는 자궁경부암의 발생률과 사망률이 훨씬 심각하다. 따라서 더 나은 진단법과 치료법이 시급하다. 인유두종바이러스가 자궁경부암 발생의 주요 원인으로 알려진 이후로 바이러스에 대한 검사가 세포검사 조직검사와 함께 자궁경부암을 진단하는데 일상적으로 쓰이고 있다. 하지만, HPV 검사에서 음성을 보이는 환자가 자궁경부암으로 발전하는 사례가 계속해서 발견되고 있다. 본 연구에서는 HPV 외에 자궁경부암의 원인으로 생각되는 인자들에 대해 분석하였다. 그 중에서도 에스트로겐 수용체 알파의 mRNA 발현양을 실시간 역전사 중합효소 연쇄반응을 통해 분석하였다. 에스트로겐 수용체 알파에 대해서는 예전부터 자궁내막을 성숙시키면서 동시에 자궁경부암의 발암 기전에 연관이 있을 것이라는 추측이 있었는데, 본 연구에서는 이에 대해 임상검체를 통해 양적 분석을 진행하였다. ROC 곡선을 바탕으로, 85%의 민감도와 75%의 특이도를 확인할 수 있었는데, 이 값은 기존의 HPV 검사법보다 유사하거나 더 높은 값이었다. 나이, 병변의 심한 정도 등을 포함한 임상 정보를 바탕으로 회귀 분석한 결과 폐경 여부와 에스트로겐 수용체 알파의 발현양이 높은 연관성을 확인하였다. 본 연구는 예비 연구의 일종으로, 추후 연구에서 가능성이 확인된 호르몬과 폐경에 관련된 유전자를 대상으로 더 많은 검체로 분석해야 할 것이다.

Abstract ▼ AI-Helper

Cervical cancer is the fourth most frequently diagnosed cancer in women worldwide. In lower Human Development Index countries, it has the second highest incidence and mortality among cancer in women. Therefore, better diagnosis and treatment systems are needed. Among them, estrogen receptor alpha ($ER-{\alpha}$) mRNA expression has been analyzed with RT-qPCR since several studies reported that $ER-{\alpha}$ is necessary in the maturation of the uterus and is related to cervical cancer. In this study, $ER-{\alpha}$ quantitative analysis was performed on various lesions and normal tissue samples. Based on the receiver operating characteristic (ROC) curve, its sensitivity and specificity were 85% and 75%, respectively, showing higher or similar results to those of conventional HPV tests. In addition, its expression level was analyzed with clinical information. With regression analysis, the R square value between the $ER-{\alpha}$ mRNA expression level and menopause status was 0.5041, indicating a strong correlation. This study was performed as part of a pilot study and suggests that $ER-{\alpha}$ is related to carcinogenesis. Future studies will examine other hormones and menopausal factors with a larger sample size.

주제어

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문제 정의

The study was investigated to understand the relevance between cervical cancer and hormone. Especially, relative expression of ER-α was analyzed among the biomarkers related to the inflow of estrogen.

제안 방법

And the relative risk was analyzed to investigate the effect of ER-α on the cervical cancer occurrence.
In fact, there are a number of articles about ER-α with clinical samples [31, 32]. However, this study was performed with quantitative analysis. And FFPE tissue was used in this study while cervical exfoliated cell is used for the study commonly.
). The analysis was conducted in normal and cancer group. As shown in Figure 3A, R² value of cancer was 0.
The tube was centrifuged for 1 min at full speed to elute the RNA. The purity and concentration of the total RNA were determined by measuring the absorbance ratio at 260 and 280 nm using a spectrophotometer (Infinite 200, Tecan, Salzburg, Austria). All preparation and handling procedures were conducted under RNase-free conditions.
Therefore, this study show ER-α is involved in the development of cancer with clinical tissue samples and it is necessary to study with menopause status.
This study was performed as part of the pilot study because ER-α mRNA expression hasn’t be analyzed quantitatively with clinical tissue sample before.
Thus, our research group analyzed ER-α expression and age with patient sample and evaluated its clinical significance.

대상 데이터

The samples were collected from cervical cancer patients and healthy subjects at Wonju Severance Christian Hospital, Wonju, Republic of Korea, from January 2010 to December 2014. All subjects provided clinical information and this study was approved by the Institutional Ethics Committee of Yonsei University Wonju College of Medicine (approval no.
YWMR-12-4-010). The study subjects were formalin fixed paraffin embedded (FFPE) cervical cancer tissue samples, those were composed of 20 squamous cell carcinoma (SCC), 20 cervical intraepithelial neoplasia grade 3 (CIN3), 20 CIN1, and 20 normal subjects (Table 1). The subjects’ age ranged from 26 to 79 years, and the median age was 48 years old.

데이터처리

A Student’s t-test and Mann-Whitney U test were used to determine the statistical significance as parametric and non-parametric statistics, respectively.
To apprehend the relationship between variables, Spearman’s rho and Kendall’s tau-b were used for the correlation analysis. Furthermore, to estimate the result, simple linear regression and multiple linear regression were used for conducting the regression analysis. For all tests, P＜0.
The correlation between ER-α expression and age was examined with regression analysis (R-squared, R2).
To apprehend the relationship between variables, Spearman’s rho and Kendall’s tau-b were used for the correlation analysis.

이론/모형

Relative gene expression was assessed using the comparative Ct method (∆∆ Ct method) [30]. The amount of target, normalized to an internal housekeeping gene, GAPDH, and relative to a calibrator, is given by 2- ∆∆Ct which was the normalized according to the following equation:

성능/효과

The histopathological diagnosis was classified as normal, cervical intraepithelial neoplasia 1 (CIN 1), cervical intraepithelial neoplasia 2 (CIN 2), cervical intraepithelial neoplasia 3 (CIN 3), adenocarcinoma (ADC), and squamous cell carcinoma (SCC). CIN1 is the least risky type and represents only mild dysplasia or abnormal cell growth.

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저자의 다른 논문 :

표제어: PCR

동의어: Packet Collision Rate

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용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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