Tzu-Ju Chen1,2,3, Chia-Lin Chou4, Yu-Feng Tian4, Cheng-Fa Yeh5, Ti-Chun Chan6,7, Hong-Lin He2,8,9, Wan-Shan Li2,3,9, Hsin-Hwa Tsai1,6, Chien-Feng Li10,11,12,13,14, Hong-Yue Lai15,16. 1. Department of Clinical Pathology, Chi Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan City, 710, Taiwan. 2. Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan. 3. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. 4. Division of Colon and Rectal Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan. 5. Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. 6. Department of Medical Research, Chi Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan City, 710, Taiwan. 7. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. 8. Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan. 9. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan. 10. Department of Clinical Pathology, Chi Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan City, 710, Taiwan. angelo.p@yahoo.com.tw. 11. Department of Medical Research, Chi Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan City, 710, Taiwan. angelo.p@yahoo.com.tw. 12. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. angelo.p@yahoo.com.tw. 13. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan. angelo.p@yahoo.com.tw. 14. Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. angelo.p@yahoo.com.tw. 15. Department of Clinical Pathology, Chi Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan City, 710, Taiwan. golddigger815@yahoo.com.tw. 16. Department of Medical Research, Chi Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan City, 710, Taiwan. golddigger815@yahoo.com.tw.
Abstract
BACKGROUND: Rectal cancer patients can conceivably obtain relief from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before resection, but the stratification of risk and clinical outcomes remains challenging. Therefore, identifying effective predictive biomarkers offers clinicians the opportunity to individually tailor early interventions, which would help optimize therapy. METHODS: Using a public rectal cancer transcriptome dataset (GSE35452), we focused on cytoskeletal protein binding (GO: 0008092)-related genes and identified FERM domain containing 3 (FRMD3) as the most significant differentially expressed gene associated with CCRT resistance. We gathered 172 tumor samples from rectal cancer patients treated with neoadjuvant CCRT accompanied by curative resection and estimated the expression level of FRMD3 using immunohistochemistry. RESULTS: The results revealed that high FRMD3 immunoexpression was remarkably associated with advanced pre-CCRT and post-CCRT tumor status (p = 0.004 and p < 0.001), pre-CCRT and post-CCRT lymph node metastasis (both p < 0.001), more perineurial invasion (p = 0.023), and a smaller extent of tumor regression (p = 0.018). High FRMD3 immunoexpression was remarkably correlated with inferior disease-specific survival (DSS) (p = 0.0001), local recurrence-free survival (LRFS) (p = 0.0003), and metastasis-free survival (MeFS) (p = 0.0023) at the univariate level. Furthermore, in multivariate analysis, high FRMD3 immunoexpression remained independently predictive of inferior DSS (p = 0.002), LRFS (p = 0.005), and MeFS (p = 0.015). CONCLUSION: These results suggest that high FRMD3 expression is related to advanced clinicopathological features and inferior therapeutic responses in rectal cancer patients treated with CCRT, validating the promising prognostic value of FRMD3 expression.
BACKGROUND: Rectal cancer patients can conceivably obtain relief from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before resection, but the stratification of risk and clinical outcomes remains challenging. Therefore, identifying effective predictive biomarkers offers clinicians the opportunity to individually tailor early interventions, which would help optimize therapy. METHODS: Using a public rectal cancer transcriptome dataset (GSE35452), we focused on cytoskeletal protein binding (GO: 0008092)-related genes and identified FERM domain containing 3 (FRMD3) as the most significant differentially expressed gene associated with CCRT resistance. We gathered 172 tumor samples from rectal cancer patients treated with neoadjuvant CCRT accompanied by curative resection and estimated the expression level of FRMD3 using immunohistochemistry. RESULTS: The results revealed that high FRMD3 immunoexpression was remarkably associated with advanced pre-CCRT and post-CCRT tumor status (p = 0.004 and p < 0.001), pre-CCRT and post-CCRT lymph node metastasis (both p < 0.001), more perineurial invasion (p = 0.023), and a smaller extent of tumor regression (p = 0.018). High FRMD3 immunoexpression was remarkably correlated with inferior disease-specific survival (DSS) (p = 0.0001), local recurrence-free survival (LRFS) (p = 0.0003), and metastasis-free survival (MeFS) (p = 0.0023) at the univariate level. Furthermore, in multivariate analysis, high FRMD3 immunoexpression remained independently predictive of inferior DSS (p = 0.002), LRFS (p = 0.005), and MeFS (p = 0.015). CONCLUSION: These results suggest that high FRMD3 expression is related to advanced clinicopathological features and inferior therapeutic responses in rectal cancer patients treated with CCRT, validating the promising prognostic value of FRMD3 expression.
Authors: Ahmedin Jemal; Freddie Bray; Melissa M Center; Jacques Ferlay; Elizabeth Ward; David Forman Journal: CA Cancer J Clin Date: 2011-02-04 Impact factor: 508.702
Authors: Barbara Zellinger; Ulrich Bodenhofer; Immanuela A Engländer; Cornelia Kronberger; Brane Grambozov; Elvis Ruznic; Markus Stana; Josef Karner; Gerd Fastner; Karl Sotlar; Felix Sedlmayer; Franz Zehentmayr Journal: Breast Cancer Date: 2021-12-05 Impact factor: 4.239