Hak-Ryul Kim1, Gyeong-Ok Lee2, Keum-Ha Choi3, Dong Kwan Kim4, Jae-Suk Ryu2, Ki-Eun Hwang1, Kook-Joo Na5, Chan Choi6, Ja Hong Kuh7, Myoung Ja Chung8, Mi-Kyoung Lee9, Hong-Seob So10, Kwon-Ha Yoon11, Min-Cheol Park12, Kyong-Suk Na2, Young-Suk Kim1, Do-Sim Park13. 1. Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 2. Department of Laboratory Medicine, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 3. Department of Pathology, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 4. Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, Seoul, 05505, Republic of Korea. 5. Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea. 6. Department of Pathology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea. 7. Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea. 8. Department of Pathology, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea. 9. Department of Thoracic and Cardiovascular Surgery, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 10. Department of Microbiology, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 11. Department of Radiology, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 12. Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, 54538, Republic of Korea. 13. 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.
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.
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.
Authors: Valentina Botti; François McNicoll; Michaela C Steiner; Florian M Richter; Anfisa Solovyeva; Marius Wegener; Oliver D Schwich; Ina Poser; Kathi Zarnack; Ilka Wittig; Karla M Neugebauer; Michaela Müller-McNicoll Journal: J Cell Biol Date: 2017-06-07 Impact factor: 10.539