혈청학적 유전자 검색 방법(SEREX)은 암 환자의 면역계를 인식하는 종양 면역유전체(Cancer Immunome)를 형성하는 수많은 종양항원의 발견을 이끌어왔다. 본 연구는 정상인의 고환 조직으로 만들어진 cDNA liabary을 사용하여 폐암환자의 혈청으로부터 40개의 종양항원을 동정하여 그 항원들을 KP-LuT-1부터 KP-LuT-40까지 명명하였다. 이들 항원 중에서 20개는 기존의 다른 종류의 암에서 분리된 것이며 20개는 본 실험에서 새롭게 동정 된 항원들이었다. 유전자 분석을 통하여 분리된 26개의 항원들은 그 단백질의 기능이 알려진 것이었고 14개의 항원들은 기능이 분석되지 않은 유전체의 산물이었다. 이들 항원 중에서 hypothetic단백질 KP-LuT-6는 정상조직에서 제한적으로 발현되었다. RT-PCR에 의한 발현분석 결과에서 16개의 정상조직 중 고환에서만 강력하게 발현 하였고 다른 조직에서는 발현되지 않으나 폐암(3/10), 위암 (3/10) 과 유방암(1/5)들에서 발현 하였다. 이 결과는 KP-LuT-6의 항원이 암 면역치료를 위한 잠재적 유전자로 사용될 수 있는 Cancer/Testis(CT) 항원과 비슷한 유전 자로 사료된다.
혈청학적 유전자 검색 방법(SEREX)은 암 환자의 면역계를 인식하는 종양 면역유전체(Cancer Immunome)를 형성하는 수많은 종양항원의 발견을 이끌어왔다. 본 연구는 정상인의 고환 조직으로 만들어진 cDNA liabary을 사용하여 폐암환자의 혈청으로부터 40개의 종양항원을 동정하여 그 항원들을 KP-LuT-1부터 KP-LuT-40까지 명명하였다. 이들 항원 중에서 20개는 기존의 다른 종류의 암에서 분리된 것이며 20개는 본 실험에서 새롭게 동정 된 항원들이었다. 유전자 분석을 통하여 분리된 26개의 항원들은 그 단백질의 기능이 알려진 것이었고 14개의 항원들은 기능이 분석되지 않은 유전체의 산물이었다. 이들 항원 중에서 hypothetic단백질 KP-LuT-6는 정상조직에서 제한적으로 발현되었다. RT-PCR에 의한 발현분석 결과에서 16개의 정상조직 중 고환에서만 강력하게 발현 하였고 다른 조직에서는 발현되지 않으나 폐암(3/10), 위암 (3/10) 과 유방암(1/5)들에서 발현 하였다. 이 결과는 KP-LuT-6의 항원이 암 면역치료를 위한 잠재적 유전자로 사용될 수 있는 Cancer/Testis(CT) 항원과 비슷한 유전 자로 사료된다.
Serological anlysis of recombinant cDNA expression libraries (SEREX) has led to identification of several categories of new antigens recognized by the immune system of cancer patients, which are referred to as the cancer immunome. We analyzed normal testis cDNA expression libraries with serumobtaine...
Serological anlysis of recombinant cDNA expression libraries (SEREX) has led to identification of several categories of new antigens recognized by the immune system of cancer patients, which are referred to as the cancer immunome. We analyzed normal testis cDNA expression libraries with serumobtained from non-small lung cancer patient and isolated 40 distinct antigen designated KP-LuT-1 through KP-LuT-40. Among these antigens 20 antigens were previously identified by SEREX analysis of other tumor types, and 20 out of 40 antigens (50%) did not match entries in Cancer Immunome Database and were considered newly identified antigens. Sequencing analysis showed that the anti-gens comprised 26 functional known proteins and 14 noble/uncharacterized gene products. Of these, the hypothetical protein KP-LuT-6 was shown tissue-restricted. RT-PCR showed it to be expressed strongly only in normal testis. In addition to normal tissues-restricted expression, KP-LuT-6 mRNA was detected in lung tumor samples(3/l0), stomach tumor samples(3/l0), and breast tumor samples(l/5), whereas not detected in colon tumor samples(O/I2). These data suggest that KP-LuT-6 is a cancer/testis (CT)-like antigen as a potential target for cancer immunotherapies.
Serological anlysis of recombinant cDNA expression libraries (SEREX) has led to identification of several categories of new antigens recognized by the immune system of cancer patients, which are referred to as the cancer immunome. We analyzed normal testis cDNA expression libraries with serumobtained from non-small lung cancer patient and isolated 40 distinct antigen designated KP-LuT-1 through KP-LuT-40. Among these antigens 20 antigens were previously identified by SEREX analysis of other tumor types, and 20 out of 40 antigens (50%) did not match entries in Cancer Immunome Database and were considered newly identified antigens. Sequencing analysis showed that the anti-gens comprised 26 functional known proteins and 14 noble/uncharacterized gene products. Of these, the hypothetical protein KP-LuT-6 was shown tissue-restricted. RT-PCR showed it to be expressed strongly only in normal testis. In addition to normal tissues-restricted expression, KP-LuT-6 mRNA was detected in lung tumor samples(3/l0), stomach tumor samples(3/l0), and breast tumor samples(l/5), whereas not detected in colon tumor samples(O/I2). These data suggest that KP-LuT-6 is a cancer/testis (CT)-like antigen as a potential target for cancer immunotherapies.
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제안 방법
A preliminary in silico mRNA expression profile and characterization of gene products identified in this study was undertaken based on the tissue distribution of expressed sequence tags (ESTs) [6], SAGE tags [4] in the Cancer Genome Anatomy Database (CGAP: http://cgap. nci.nih. gov/), Massively Parallel Signature sequencing tags (MPSS: https://www2.licr.org/BRAIN/) and the information contained in the GeneCards database (http:// bioinfo.weizmann.ac.il/cards-bin/).
대상 데이터
Human tumor tissues and sera were obtained from Department of Surgery and made a diagnosis and staging by Department of Pathology, Pusan National University Hospital. The tissues were frozen in liquid nitrogen and stored at -80℃ untill use.
이론/모형
In this study, the SEREX methodology is applied to isolate lung cancer associated antigens. For this purpose, sera from lung cancer patient were used to screen cDNA libraries derived from normal testis and the 40 distinct lung cancer antigens were identified.
성능/효과
In conclusion, we have used a combined bioinformatics and SEREX based screening for cancer antigens and identified at least one novel potential target for cancer therapy, hypothetical protein C6ORF10, KP-LuT-6. This gene is aberrantly expressed in lung, stomach and breast cancers and is thus potentially of widespread utility.
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