title: SRSF5: a novel marker for small-cell lung cancer and pleural metastatic cancer.
abstract: SR-splicing factors (SRSFs) play important roles in oncogenesis. However, the expression of SRSF 5-7 proteins in lung cancer (LC) is unclear, and their use in the diagnosis of pleural diseases has never been assessed. We evaluated SRSF 5-7 protein levels in LC and their diagnostic potential for cancer cells in lung and pleural effusion (PE) and, for the dysregulated SRSFs, investigated their neutralization effect on LC.
  
  
  
  SRSF 5-7 levels in lung tissue and PE cell lysate samples (n=453) were compared with the results of conventional tumor markers. Knockdown of SRSF gene expression was performed using small interfering RNAs on small-cell LC (SCLC) cell lines.
  
  
  
  In lung tissue analysis, SRSF 5-7 levels were up-regulated in LC samples compared with non-tumoral lung tissue samples; they were markedly higher in SCLC than in adenocarcinoma or squamous cell carcinoma. SRSF5 showed the highest detection accuracy (89%) for total LC, and it was superior to that (74%) of carcinoembryonic antigen [CEA, a commonly used non-SCLC (NSCLC) marker]. Notably, the detection accuracies of the three SRSFs for SCLC were all 100% and higher than that (69%) of a pro-gastrin-releasing peptide (a well-known SCLC marker). In PE cell analysis, the detection accuracy (86%) of SRSF5 for malignant cells was highest among SRSFs and comparable to that (83%) of CEA. SRSF5 additionally detected 70% of CEA-missed non-NSCLC cases. Down-regulation of the SRSFs induced mild (SRSF5 and SRSF7) to remarkably (SRSF6) reduced cell proliferation.
  
  
  
  Our results demonstrated the up-regulated expression of SRSF 5-7 proteins in LC with much more profound up-regulation in SCLC than in NSCLC and suggest that up-regulation of the SRSFs is related to SCLC proliferation. Moreover, we identified SRSF5 as a novel detection marker for SCLC and pleural metastatic cancer cells.
authors: Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Hak-Ryul
authors: HR
authors: Kim
authors: Department of Laboratory Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Gyeong-Ok
authors: GO
authors: Lee
authors: Department of Pathology, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Keum-Ha
authors: KH
authors: Choi
authors: Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, Seoul, 05505, Republic of Korea.
authors: Dong Kwan
authors: DK
authors: Kim
authors: Department of Laboratory Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Jae-Suk
authors: JS
authors: Ryu
authors: Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Ki-Eun
authors: KE
authors: Hwang
authors: Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea.
authors: Kook-Joo
authors: KJ
authors: Na
authors: Department of Pathology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea.
authors: Chan
authors: C
authors: Choi
authors: Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea.
authors: Ja Hong
authors: JH
authors: Kuh
authors: Department of Pathology, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea.
authors: Myoung Ja
authors: MJ
authors: Chung
authors: Department of Thoracic and Cardiovascular Surgery, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Mi-Kyoung
authors: MK
authors: Lee
authors: Department of Microbiology, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Hong-Seob
authors: HS
authors: So
authors: Department of Radiology, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Kwon-Ha
authors: KH
authors: Yoon
authors: Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Min-Cheol
authors: MC
authors: Park
authors: Department of Laboratory Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Kyong-Suk
authors: KS
authors: Na
authors: Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors: Young-Suk
authors: YS
authors: Kim
authors: Department of Laboratory Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea; Wonkwang Institute of Clinical Medicine, Wonkwang University Hospital, Iksan, 54538, Republic of Korea. Electronic address: emailds@hanmail.net.
authors: Do-Sim
authors: DS
authors: Park
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D010997:Pleural Neoplasms / Q000378:metabolism* / Q000556:secondary*; D011994:Recombinant Proteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D010446:Peptide Fragments; D011994:Recombinant Proteins; C087079:pro-gastrin-releasing peptide (31-98); D000068103:Serine-Arginine Splicing Factors
keywords: Carcinoembryonic antigen; Pleural effusion; SRSF5; Small-cell lung cancer; Splicing factor