Comparative expression patterns and diagnostic efficacies of SR splicing factors and HNRNPA1 in gastric and colorectal cancer.
Serine/arginine-rich splicing factors (SRSFs) and HNRNPA1 have oncogenic properties. However, their proteomic expressions and practical priority in gastric cancer (GC) and colorectal cancer (CRC) are mostly unknown. To apply SFs in clinics, effective marker selection and characterization of properties in the target organ are essential.



We concurrently analyzed SRSF1, 3, and 5-7, and HNRNPA1, together with the conventional tumor marker carcinoembryonic antigen (CEA), in stomach and colorectal tissue samples (n = 420) using semiquantitative immunoblot, subcellular fractionation, and quantitative real-time polymerase chain reaction methods.



In the semiquantitative immunoblot analysis, HNRNPA1 and SRSF7 levels were significantly higher in GC than in gastric normal mucosa, and SRSF7 levels were higher in intestinal-type compared with diffuse-type of gastric adenocarcinoma. Of the SFs, only HNRNPA1 presented greater than 50 % upregulation (cancer/normal mucosa > 2-fold) incidences and CEA-comparable, acceptable (>70 %) detection accuracy (74 %) for GC. All SF protein levels were significantly higher in CRC than in colorectal normal mucosa, and HNRNPA1 levels were higher in low-stage CRC compared with high-stage CRC. Among the SFs, HNRNPA1 and SRSF3 presented the two highest upregulation incidences (88 % and 74 %, respectively) and detection accuracy (90 % and 84 %, respectively) for CRC. The detection accuracy of HNRNPA1 was comparable to that of CEA in low (≤ II)-stage CRC but was inferior to that of CEA in high (>II)-stage CRC. Extranuclear distributions of HNRNPA1 and SRSF6 (cytosol/microsome) differed from those of other SRSFs (membrane/organelle) in both cancers. In an analysis of the six SF mRNAs, all mRNAs presented unacceptable detection accuracies (≤70 %) in both cancers, and all mRNAs except SRSF6 were disproportionate to the corresponding protein levels in GC.



Our results provide a comprehensive insight into the six SF expression profiles in GC and indicate that, among the SFs, HNRNPA1, but not HNRNPA1 mRNA, is the most effective, novel GC marker. Regardless of the good to excellent detection accuracy of SRSF3 and HNRNPA1 in CRC, the SFs have lower practical priority than CEA, especially for high-stage CRC detection.
Department of Surgery, School of Medicine, Wonkwang University, Iksan, South Korea.
Won Cheol
WC
Park
Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, South Korea.
Hak-Ryul
HR
Kim
Department of Surgery, School of Medicine, Wonkwang University, Iksan, South Korea.
Dong Baek
DB
Kang
Department of Laboratory Medicine, School of Medicine, Wonkwang University, 895 Muwang-ro, Iksan, 54538, Republic of Korea.|Center for Metabolic Function Regulation, Institute of Wonkwang Medical Science and Institute of Wonkwang Clinical Medicine, School of Medicine, Wonkwang University, Iksan, Korea.
Jae-Suk
JS
Ryu
Department of Pathology, School of Medicine, Wonkwang University, Iksan, Korea.
Keum-Ha
KH
Choi
Department of Laboratory Medicine, School of Medicine, Wonkwang University, 895 Muwang-ro, Iksan, 54538, Republic of Korea.|Center for Metabolic Function Regulation, Institute of Wonkwang Medical Science and Institute of Wonkwang Clinical Medicine, School of Medicine, Wonkwang University, Iksan, Korea.
Gyeong-Ok
GO
Lee
Department of Pathology, School of Medicine, Wonkwang University, Iksan, Korea.
Ki Jung
KJ
Yun
Department of Surgery, School of Medicine, Wonkwang University, Iksan, South Korea.
Keun Young
KY
Kim
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangu, Korea.
Raekil
R
Park
Department of Radiology, School of Medicine, Wonkwang University, Iksan, Korea.
Kwon-Ha
KH
Yoon
Department of Laboratory Medicine, School of Medicine, Wonkwang University, 895 Muwang-ro, Iksan, 54538, Republic of Korea.
Ji-Hyun
JH
Cho
Department of Laboratory Medicine, School of Medicine, Wonkwang University, 895 Muwang-ro, Iksan, 54538, Republic of Korea.
Young-Jin
YJ
Lee
Department of Pathology, School of Medicine, Wonkwang University, Iksan, Korea.
Soo-Cheon
SC
Chae
Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Korea.
Min-Cheol
MC
Park
Department of Laboratory Medicine, School of Medicine, Wonkwang University, 895 Muwang-ro, Iksan, 54538, Republic of Korea. emailds@hanmail.net.|Center for Metabolic Function Regulation, Institute of Wonkwang Medical Science and Institute of Wonkwang Clinical Medicine, School of Medicine, Wonkwang University, Iksan, Korea. emailds@hanmail.net.
Do-Sim
DS
Park
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D002272:Carcinoembryonic Antigen; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D010750:Phosphoproteins; C491388:SRSF3 protein, human; C489470:SRSF6 protein, human; C000595780:SRSF7 protein, human; C000619656:hnRNPA1 protein, human; D000068103:Serine-Arginine Splicing Factors
Carcinoembryonic antigen; Gastric cancer; HNRNPA1; SRSF7; Splicing factor