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|Ref Type||Journal Article|
|Authors||Mesker WE, Liefers GJ, Junggeburt JM, van Pelt GW, Alberici P, Kuppen PJ, Miranda NF, van Leeuwen KA, Morreau H, Szuhai K, Tollenaar RA, Tanke HJ|
|Title||Presence of a high amount of stroma and downregulation of SMAD4 predict for worse survival for stage I-II colon cancer patients.|
|Journal||Cellular oncology : the official journal of the International Society for Cellular Oncology|
|Abstract Text||For stage I-II colon cancer a significant number (5-25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment. Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: beta-catenin, TGF-beta-R2 and SMAD4.In a retrospective study of 135 patients with stage I-II colon cancer, the amount of stroma was estimated on routine haematoxylin-eosin stained histological sections. Sections were also immunohistochemically stained for beta-catenin, TGF-beta-R2 and SMAD4.Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p<0.001, HZ 2.73, CI 1.73-4.30; DFS p<0.001, HZ 2.43, CI 1.55-3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p=0.008, HZ 7.98, CI 4.12-15.44, DFS p=0.005, HZ 6.57, CI 3.43-12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13-13.82, p<0.001).Conventional haematoxylin-eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor-stroma ratio. The combination of analyzing the tumor-stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.|
|Molecular Profile||Treatment Approach|
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|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|SMAD4 dec exp||colorectal cancer||not applicable||N/A||Clinical Study||Prognostic||In clinical and meta-analyses, decreased expression of Smad4 was correlated with poor prognosis in colorectal cancer (PMID: 25749173, PMID: 19478385, PMID: 25681512, PMID: 26861460).||25749173 19478385 26861460 25681512|