Prognostic value of SMAD4 in resectable pancreatic cancer
Open accessAbstract
Introduction: The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene expression in PC and its prognosis remains inconclusive. The aim of this study was to evaluate the association between loss of SMAD4 expression and the outcome of resectable PC. Materials and Methods: A systematic review of the relevant electronic databases was conducted between SMAD4 expression and the outcome of PC patients until December 2020, including PubMed, Web of Science, and the China Journal Net. A meta-analysis was performed using STATA 12.0 and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 gene expression and the prognosis of PC patients. Results: Twelve studies were included. Our meta-analysis illustrated that there were no significant associations between the loss of SMAD4 gene expression and overall survival in resectable PC (HR=1.38, 95% CI 0.98–1.81). In addition, there was no evidence of publication bias, as showed by Begg's and Egger's test. There was no correlation between the loss of SMAD4 expression and local recurrence (OR=0.97, 95% CI 0.52–1.80, p=0.914), while the loss of SMAD4 gene expression was associated with increased risk of distant recurrence (OR=1.36, 95% CI 1.08–1.70, p=0.008). Conclusions: After PC resection, the loss of SMAD4 gene expression was correlated with higher risk of distant recurrence, but not with local recurrence nor overall survival.
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Reported results about the prognostic value of SMAD4 have been inconsistent.
“SMAD4 is a tumor suppressor gene, and reported results about the prognostic value of SMAD4 have been inconsistent39,60–62.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [62]
A separately reported meta-analysis did not show an association between SMAD4 mutation and OS.
“While an association between SMAD4 inactivation in resected PDAC and poor prognosis has been reported, a separately reported meta-analysis did not show association between SMAD4 mutation and OS61,62.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [62]
An association between SMAD4 inactivation in resected PDAC and poor prognosis has been reported.
“While an association between SMAD4 inactivation in resected PDAC and poor prognosis has been reported, a separately reported meta-analysis did not show association between SMAD4 mutation and OS61,62.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [62]
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Cites
Stang, A. (2010) · European Journal of Epidemiology · doi:10.1007/s10654-010-9491-z · Cited by 17,396 · see citing works
Siegel, R. L., Miller, K. D., & Jemal, A. (2018) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21442 · Cited by 16,632 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2010) · International Journal of Surgery · doi:10.1016/j.ijsu.2010.02.007 · Cited by 12,156 · see citing works
Practical methods for incorporating summary time-to-event data into meta-analysis.
Tierney, J. F., Stewart, L. A., Ghersi, D., Burdett, S., & Sydes, M. R. (2007) · Trials · doi:10.1186/1745-6215-8-16 · Cited by 6,208 · see citing works
Vincent, A., Herman, J. M., Schulick, R., Hruban, R. H., & Goggins, M. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62307-0 · Cited by 2,613 · see citing works
TGF-β and epithelial-to-mesenchymal transitions
Zavadil, J., & Böttinger, E. P. (2005) · Oncogene · doi:10.1038/sj.onc.1208927 · Cited by 1,576 · see citing works
Neoptolemos, J. P., Stocken, D. D., Bassi, C., Ghaneh, P., Cunningham, D., Goldstein, D., Padbury, R., Moore, M. J., Gallinger, S., Mariette, C., et al. (2010) · JAMA · doi:10.1001/jama.2010.1275 · Cited by 1,395 · see citing works
Iacobuzio-Donahue, C. A., Fu, B., Yachida, S., Luo, M., Abe, H., Henderson, C. M., Vilardell, F., Wang, Z., Keller, J. W., Banerjee, P., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.7188 · Cited by 1,081 · see citing works
TGF-β Tumor Suppression through a Lethal EMT
David, C. J., Huang, Y.-H., Chen, M., Su, J., Zou, Y., Bardeesy, N. M., Iacobuzio–Donahue, C. A., & Massagué, J. (2016) · Cell · doi:10.1016/j.cell.2016.01.009 · Cited by 597 · see citing works
Deckers, M., van Dinther, M., Buijs, J., Que, I., Löwik, C., van der Pluijm, G., & ten Dijke, P. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3560 · Cited by 379 · see citing works
Herman, J. M., Swartz, M. J., Hsu, C. C.-C., Winter, J. M., Pawlik, T. M., Sugar, E. A., Robinson, R., Laheru, D. A., Jaffee, E. M., Hruban, R. H., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.8469 · Cited by 375 · see citing works
<i>SMAD4</i> Gene Mutations Are Associated with Poor Prognosis in Pancreatic Cancer
Blackford, A., Serrano, O. K., Wolfgang, C. L., Parmigiani, G., Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Eshleman, J. R., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0227 · Cited by 371 · see citing works
Regine, W. F., Winter, K. A., Abrams, R. A., Safran, H. P., Hoffman, J. P., Konski, A. A., Benson, A. B., Macdonald, J. S., Rich, T. A., & Willett, C. G. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1630-6 · Cited by 311 · see citing works
(2001) · PubMed · Cited by 309 · see citing works
Crane, C. H., Varadhachary, G. R., Yordy, J. S., Staerkel, G. A., Javle, M. M., Safran, H., Haque, W., Hobbs, B. D., Krishnan, S., Fleming, J. B., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.8038 · Cited by 288 · see citing works
Oshima, M., Okano, K., Muraki, S., Haba, R., Maeba, T., Suzuki, Y., & Yachida, S. (2013) · Annals of Surgery · doi:10.1097/sla.0b013e3182827a65 · Cited by 236 · see citing works
Antimetastatic Role of Smad4 Signaling in Colorectal Cancer
Zhang, B., Halder, S. K., Kashikar, N., Cho, Y., Datta, A., Gorden, D. L., & Datta, P. K. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.11.004 · Cited by 221 · see citing works
<i>DPC4</i>/Smad4 Expression and Outcome in Pancreatic Ductal Adenocarcinoma
Biankin, A. V., Morey, A. L., Lee, C.-S., Kench, J. G., Biankin, S. A., Hook, H. C., Head, D. R., Hugh, T. B., Sutherland, R. L., & Henshall, S. M. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.12.063 · Cited by 163 · see citing works
Biomarkers of TGF-β Signaling Pathway and Prognosis of Pancreatic Cancer
Javle, M. M., Li, Y., Tan, D., Dong, X., Chang, P., Kar, S., & Li, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085942 · Cited by 130 · see citing works
Kang, Y. K., Kim, W. H., & Jang, J. J. (2002) · Human Pathology · doi:10.1053/hupa.2002.127444 · Cited by 116 · see citing works
Maitra, A., Molberg, K. H., Albores‐Saavedra, J., & Lindberg, G. M. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64625-1 · Cited by 112 · see citing works
Sun, G., Li, Z., Wang, W., Chen, Z., Zhang, L., Li, Q., Wei, S., Li, B., Xu, J., Chen, L., et al. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1408-0 · Cited by 85 · see citing works
Failure Patterns in Resected Pancreas Adenocarcinoma
Winter, J. M., Tang, L. H., Klimstra, D. S., Liu, W., Linkov, I., Brennan, M. F., D'Angelica, M. I., DeMatteo, R. P., Fong, Y., Jarnagin, W. R., et al. (2013) · Annals of Surgery · doi:10.1097/sla.0b013e31827fe9ce · Cited by 77 · see citing works
Bachet, J., Maréchal, R., Demetter, P., Bonnetain, F., Couvelard, A., Svrcek, M., Bardier–Dupas, A., Hammel, P. R., Sauvanet, A., Louvet, C., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mdr617 · Cited by 73 · see citing works
SMAD4 Expression Predicts Local Spread and Treatment Failure in Resected Pancreatic Cancer
Yamada, S., Fujii, T., Shimoyama, Y., Kanda, M., Nakayama, G., Sugimoto, H., Koike, M., Nomoto, S., Fujiwara, M., Nakao, A., et al. (2015) · Pancreas · doi:10.1097/mpa.0000000000000315 · Cited by 71 · see citing works
Shin, S. H., Kim, H. J., Hwang, D. W., Lee, J. H., Song, K. B., Jun, E., Shim, I. K., Hong, S.-M., Kim, H. J., Park, K.-M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.14901 · Cited by 57 · see citing works
Molecular pathology of pancreatic cancer
Saiki, Y., & Horii, A. (2014) · Pathology International · doi:10.1111/pin.12114 · Cited by 56 · see citing works
Hua, Z. (2003) · World Journal of Gastroenterology · doi:10.3748/wjg.v9.i12.2764 · Cited by 55 · see citing works
Singh, P., Srinivasan, R., & Wig, J. D. (2012) · Pancreas · doi:10.1097/mpa.0b013e318247d6af · Cited by 53 · see citing works
Tanaka, T., Watanabe, T., Kazama, Y., Tanaka, J., Kanazawa, T., Kazama, S., & Nagawa, H. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603460 · Cited by 50 · see citing works
Boone, B. A., Sabbaghian, S., Zenati, M. S., Marsh, J. W., Moser, A. J., Zureikat, A. H., Singhi, A. D., Zeh, H. J., & Krasinskas, A. M. (2014) · Journal of Surgical Oncology · doi:10.1002/jso.23606 · Cited by 49 · see citing works
RhoT1 and Smad4 Are Correlated with Lymph Node Metastasis and Overall Survival in Pancreatic Cancer
Jiang, H., He, C., Geng, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042234 · Cited by 45 · see citing works
Ottenhof, N. A., Morsink, F. H. M., ten Kate, F. J. W., Noorden, C. J. F. V., & Offerhaus, G. J. A. (2012) · Cellular Oncology · doi:10.1007/s13402-012-0072-x · Cited by 38 · see citing works
Herman, J. M., Jabbour, S. K., Lin, S. H., Deek, M. P., Hsu, C. C.-C., Fishman, E. K., Kim, S., Cameron, J. L., Chekmareva, M. A., Laheru, D. A., et al. (2018) · Pancreas · doi:10.1097/mpa.0000000000000985 · Cited by 34 · see citing works
Khorana, A. A., Hu, Y. C., Ryan, C., et al. (2005) · Journal of Gastrointestinal Surgery · doi:10.1016/j.gassur.2005.06.021 · Cited by 30 · see citing works
Xu, J.-Z., Wang, W.-Q., Zhang, W.-H., Xu, H.-X., Gao, H.-L., Zhang, S.-R., Wu, C.-T., Li, S., Li, H., Xu, J., et al. (2019) · Journal of Cancer · doi:10.7150/jca.30883 · Cited by 19 · see citing works
Tumoral epithelial and stromal expression of SMAD proteins in pancreatic ductal adenocarcinomas
Handra‐Luca, A., Hammel, P. R., Sauvanet, A., Ruszniewski, P. B., & Couvelard, A. (2012) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1007/s00534-012-0518-6 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Shen J, Gao SZ, Wang H, Shi XH, Li B, Pan YQ, Shen S, Shao Z, Guo SW, Jin G. Prognostic value of important driver gene mutations in pa- tients with radical resection of pancreatic cancer. Zhonghua Wai Ke Za Zhi. 2019; 57: 840-847.
- Toga T, Nio Y, Hashimoto K, Higami T, Maruyama R. The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome. Anticancer Res. 2004; 24: 1173-1178.
- Wilentz RE, Iacobuzio-Donahue CA, Argani P. Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 in- activation occurs late in neoplastic progression. Cancer Res. 2000; 60: 2002-2006.
Cited by
Sorted by citations
Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma
Yousef, A., Yousef, M., Chowdhury, S., Abdilleh, K., Knafl, M., Edelkamp, P., Alfaro-Munoz, K., Chacko, R., Peterson, J., Smaglo, B. G., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00505-0 · Cited by 93 · see citing works
- Authors
- Su, H., & Wang, C.
- Affiliations
- Ningbo No. 2 Hospital (CN)
- First Affiliated Hospital of Jinan University (CN)
- Corresponding author
- Su, Hui
- Venue
- Postępy Higieny i Medycyny Doświadczalnej
- Publisher
- Walter de Gruyter GmbH
- Published
- 2022-01-01
- Volume
- 76
- Issue
- 1
- Pages
- 324-332
- ISSN
- 0032-5449 (ISSN-L)
- 1732-2693
- OpenAlex
- W4292559526
- Cited by
- 1
- References
- 37
- Citations by year
- 2024: 1
- FWCI
- 0.11
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Postępy Higieny i Medycyny Doświadczalnej (publishedVersion, cc-by-nc-nd)
- Funders
- Natural Science Foundation of Ningbo (2019A610215)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- SMAD4, pancreatic cancer, resectable pancreatic cancer, gene expression loss, prognostic factors, overall survival, local recurrence, distant recurrence, pancreaticoduodenectomy
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