SRSF5: a novel marker for small-cell lung cancer and pleural metastatic cancer. (September 2016)

• Record Type: Journal Article
• Authors: Kim, Hak-Ryul; Lee, Gyeong-Ok; Choi, Keum-Ha; Kim, Dong Kwan; Ryu, Jae-Suk; Hwang, Ki-Eun; Na, Kook-Joo; Choi, Chan; Kuh, Ja Hong; Chung, Myoung Ja; Lee, Mi-Kyoung; So, Hong-Seob; Yoon, Kwon-Ha; Park, Min-Cheol; Na, Kyong-Suk; Kim, Young-Suk; Park, Do-Sim
• Is Part Of: Lung cancer. Volume 99(2016)
• Page Start: 57
• Page End: 65
• Publication Date: 2016-09
• Subjects: SRSF5 -- Small-cell lung cancer -- Pleural effusion -- Splicing factor -- Carcinoembryonic antigen; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.05.018
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: We observed upregulation of SRSF 5–7 proteins in SCLC tissue for the first time. SRSF 5–7 protein levels in SCLC were higher than in ADC or SQC types of NSCLC. SRSFs 5–7 detected SCLC in the lung more efficiently than CEA or proGRP. SRSF5 showed great diagnostic potential for SCLC and extrapulmonary cancer in PE. SRSF5 is a novel marker for SCLC and extrapulmonary pleural metastatic cancer. Abstract: Objectives: 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. Materials and methods: 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. Results: 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. Conclusions: 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.