Invited Commentary

Abstract

The study by Wen and colleagues [1Wen J. Hu Y. Luo K.J. Yang H. Zhang S.S. Fu J.H. Positive TAK1 expression has an unfavorable impact on survival in T3N1-3M0 esophageal squamous cell carcinomas.Ann Thorac Surg. 2013; 95: 285-291Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar] examined the clinical and prognostic significance of TAK1 expression in resectable T3N1-3M0 esophageal squamous cell carcinomas (ESCC). They found that increased expression of TAK1 was correlated with pathological N status and poor disease-free survival and overall survival. The results are interesting and may have some clinical significance for future studies and practice. As with any other new staging system, different voices have been emerging concerning the N category in the seventh edition of the Union Internationale Contre le Cancer/American Joint Cancer Committee for esophageal cancers, especially squamous cell carcinoma, since its publication in 2009 [2Gertler R. Stein H.J. Langer R. et al.Long-term outcome of 2920 patients with cancers of the esophagus and esophagogastric junction: evaluation of the new Union Internationale Contre le Cancer/American Joint Cancer Committee staging system.Ann Surg. 2011; 253: 689-698Crossref PubMed Scopus (126) Google Scholar, 3Yang H.X. Wei J.C. Xu Y. et al.Modification of nodal categories in the seventh American Joint Committee on cancer staging system for esophageal squamous cell carcinoma in Chinese patients.Ann Thorac Surg. 2011; 92: 216-224Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 4Xu Q.R. Zhuge X.P. Zhang H.L. et al.The N-classification for esophageal cancer staging: should it be based on number, distance, or extent of the lymph node metastasis?.World J Surg. 2011; 35: 1303-1310Crossref PubMed Scopus (37) Google Scholar]. The difficulty in defining accurately the number of involved lymph nodes even after operation, let alone preoperatively or in case of a nonsurgical treatment setting, has been raised repeatedly as a major problem. It is thus sometimes difficult to accurately stage and direct patients into different treatment groups based purely on anatomic findings. Although the specific role of TAK1 in the development and progression of ESCC remains to be investigated, the findings of this study, along with the results from many others, suggest that in addition to the current TNM staging system, nonanatomic factors such as potential biomarkers may be included in prognostic grouping. One would envision examining TAK1 expression in pretreatment endoscopic biopsy specimens or even in blood samples, and perhaps using TAK1 expression as a surrogate for lymph node metastases. As a further step, TAK1 or some other biomarkers identified could perhaps be used to decide surgical indication or guide the use of neoadjuvant therapies.The management of cancerous diseases has entered into an era of individualized treatment, thanks to closely related clinical and laboratory studies, including the current one. It is now possible and maybe even more effective to personalize therapies on the basis of bioinformation of tumors. The inclusion of epidermal growth factor receptor (EGFR) mutation as a grouping factor into the lung cancer staging system is one good example. Unfortunately, in esophageal cancers, no specific biomarker has proved to be as useful as EGFR in lung cancer. Most studies similar to this one still stand at the initial step of prognostic power analysis. In fact, a quick search of PubMed revealed that even the same authors have already published a series of studies on biomarkers related to ESCC [5Liang Y. Hou X. Cui Q. et al.Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma.J Transl Med. 2012; 10: 73Crossref PubMed Scopus (27) Google Scholar, 6Luo K.J. Wen J. Xie X. et al.Prognostic relevance of Id-1 expression in patients with resectable esophageal squamous cell carcinoma.Ann Thorac Surg. 2012; 93: 1682-1688Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 7Liu Q.W. Fu J.H. Luo K.J. et al.Identification of EGFR and KRAS mutations in Chinese patients with esophageal squamous cell carcinoma.Dis Esophagus. 2011; 24: 1442-2050Crossref Scopus (27) Google Scholar, 8Luo K.J. Hu Y. Wen J. Fu J.H. CyclinD1, p53, E-cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: a tissue array analysis.J Surg Oncol. 2011; 104: 236-243Crossref PubMed Scopus (27) Google Scholar, 9Zhang X. Lin P. Zhu Z.H. et al.Expression profiles of early esophageal squamous cell carcinoma by cDNA microarray.Cancer Genet Cytogenet. 2009; 194: 23-29Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 10Huang W.Z. Fu J.H. Wang D.K. et al.Overexpression of cyclooxygenase-2 is associated with chemoradiotherapy resistance and prognosis in esophageal squamous cell carcinoma patients.Dis Esophagus. 2008; 21: 679-684Crossref PubMed Scopus (28) Google Scholar]. Thus, more effort is needed to go deeper into transformational research so as to optimize therapeutic decision making. And it would be interesting to pool the results currently available to see whether there is enough evidence to actually start modifying management strategy accordingly. The study by Wen and colleagues [1Wen J. Hu Y. Luo K.J. Yang H. Zhang S.S. Fu J.H. Positive TAK1 expression has an unfavorable impact on survival in T3N1-3M0 esophageal squamous cell carcinomas.Ann Thorac Surg. 2013; 95: 285-291Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar] examined the clinical and prognostic significance of TAK1 expression in resectable T3N1-3M0 esophageal squamous cell carcinomas (ESCC). They found that increased expression of TAK1 was correlated with pathological N status and poor disease-free survival and overall survival. The results are interesting and may have some clinical significance for future studies and practice. As with any other new staging system, different voices have been emerging concerning the N category in the seventh edition of the Union Internationale Contre le Cancer/American Joint Cancer Committee for esophageal cancers, especially squamous cell carcinoma, since its publication in 2009 [2Gertler R. Stein H.J. Langer R. et al.Long-term outcome of 2920 patients with cancers of the esophagus and esophagogastric junction: evaluation of the new Union Internationale Contre le Cancer/American Joint Cancer Committee staging system.Ann Surg. 2011; 253: 689-698Crossref PubMed Scopus (126) Google Scholar, 3Yang H.X. Wei J.C. Xu Y. et al.Modification of nodal categories in the seventh American Joint Committee on cancer staging system for esophageal squamous cell carcinoma in Chinese patients.Ann Thorac Surg. 2011; 92: 216-224Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 4Xu Q.R. Zhuge X.P. Zhang H.L. et al.The N-classification for esophageal cancer staging: should it be based on number, distance, or extent of the lymph node metastasis?.World J Surg. 2011; 35: 1303-1310Crossref PubMed Scopus (37) Google Scholar]. The difficulty in defining accurately the number of involved lymph nodes even after operation, let alone preoperatively or in case of a nonsurgical treatment setting, has been raised repeatedly as a major problem. It is thus sometimes difficult to accurately stage and direct patients into different treatment groups based purely on anatomic findings. Although the specific role of TAK1 in the development and progression of ESCC remains to be investigated, the findings of this study, along with the results from many others, suggest that in addition to the current TNM staging system, nonanatomic factors such as potential biomarkers may be included in prognostic grouping. One would envision examining TAK1 expression in pretreatment endoscopic biopsy specimens or even in blood samples, and perhaps using TAK1 expression as a surrogate for lymph node metastases. As a further step, TAK1 or some other biomarkers identified could perhaps be used to decide surgical indication or guide the use of neoadjuvant therapies. The management of cancerous diseases has entered into an era of individualized treatment, thanks to closely related clinical and laboratory studies, including the current one. It is now possible and maybe even more effective to personalize therapies on the basis of bioinformation of tumors. The inclusion of epidermal growth factor receptor (EGFR) mutation as a grouping factor into the lung cancer staging system is one good example. Unfortunately, in esophageal cancers, no specific biomarker has proved to be as useful as EGFR in lung cancer. Most studies similar to this one still stand at the initial step of prognostic power analysis. In fact, a quick search of PubMed revealed that even the same authors have already published a series of studies on biomarkers related to ESCC [5Liang Y. Hou X. Cui Q. et al.Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma.J Transl Med. 2012; 10: 73Crossref PubMed Scopus (27) Google Scholar, 6Luo K.J. Wen J. Xie X. et al.Prognostic relevance of Id-1 expression in patients with resectable esophageal squamous cell carcinoma.Ann Thorac Surg. 2012; 93: 1682-1688Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 7Liu Q.W. Fu J.H. Luo K.J. et al.Identification of EGFR and KRAS mutations in Chinese patients with esophageal squamous cell carcinoma.Dis Esophagus. 2011; 24: 1442-2050Crossref Scopus (27) Google Scholar, 8Luo K.J. Hu Y. Wen J. Fu J.H. CyclinD1, p53, E-cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: a tissue array analysis.J Surg Oncol. 2011; 104: 236-243Crossref PubMed Scopus (27) Google Scholar, 9Zhang X. Lin P. Zhu Z.H. et al.Expression profiles of early esophageal squamous cell carcinoma by cDNA microarray.Cancer Genet Cytogenet. 2009; 194: 23-29Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 10Huang W.Z. Fu J.H. Wang D.K. et al.Overexpression of cyclooxygenase-2 is associated with chemoradiotherapy resistance and prognosis in esophageal squamous cell carcinoma patients.Dis Esophagus. 2008; 21: 679-684Crossref PubMed Scopus (28) Google Scholar]. Thus, more effort is needed to go deeper into transformational research so as to optimize therapeutic decision making. And it would be interesting to pool the results currently available to see whether there is enough evidence to actually start modifying management strategy accordingly. Positive Transforming Growth Factor-β Activated Kinase-1 Expression Has an Unfavorable Impact on Survival in T3N1-3M0 Esophageal Squamous Cell CarcinomasThe Annals of Thoracic SurgeryVol. 95Issue 1PreviewTransforming growth factor-β activated kinase-1 (TAK1) is a serine/threonine kinase in the mitogen-activated protein kinase kinase family. Previous studies have reported the role of TAK1 in cancer occurrence and progression; however, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) has not been elucidated. We investigated the correlation of TAK1 expression and clinical outcome in T3N1-3M0 surgically resected ESCCs. Full-Text PDF