A Combined ULBP2 and SEMA5A Expression Signature as a Prognostic and Predictive Biomarker for Colon Cancer

Demirkol, Seçil; Gömceli, İsmail; Isbilen, Murat; Dayanç, Barış Emre; Tez, Mesut; Bostancı, Erdal Birol; Turhan, Nesrin; Akoğlu, Musa; Özyerli, Ezgi; Durdu, Sevi; Konu, Özlen; Nissan, Aviram; Gönen, Mithat; Gure, Ali Osmay

doi:10.7150/jca.17872

Cited by 30 publications

(27 citation statements)

References 37 publications

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“…In line with our earlier findings 27 , we show here for the first time in vitro, that Lapatinib and Midostaurin are candidates for such combination therapy, as they target selectively either NS/E or CS/M cells, respectively. Even though EMT might be a signature shared among tumor types, combination treatment suggestions obtained for breast cancer in this study are different from those we found for other tumor types, such as colon cancer and melanoma 68,69 . One explanation for this can be that NS/E and CS/M cell types defined for tumors originating from different tissues actually define different phenotypes in the EMT or plasticity scale.…”

Section: Discussioncontrasting

confidence: 99%

A Stemness and EMT Based Gene Expression Signature Identifies Phenotypic Plasticity and is A Predictive but Not Prognostic Biomarker for Breast Cancer

et al. 2020

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Aims: Molecular heterogeneity of breast cancer results in variation in morphology, metastatic potential and response to therapy. We previously showed that breast cancer cell line sub-groups obtained by a clustering approach using highly variable genes overlapped almost completely with sub-groups generated by a drug cytotoxicity-profile based approach. Two distinct cell populations thus identified were CSC(cancer stem cell)-like and non-CSC-like. In this study we asked whether an mRNA based gene signature identifying these two cell types would explain variation in stemness, EMT, drug sensitivity, and prognosis in silico and in vitro. Main methods: In silico analyses were performed using publicly available cell line and patient tumor datasets. In vitro analyses of phenotypic plasticity and drug responsiveness were obtained using human breast cancer cell lines. Key findings: We find a novel gene list (CNCL) that can generate both categorical and continuous variables corresponding to the stemness/EMT (epithelial to mesenchymal transition) state of tumors. We are presenting a novel robust gene signature that unites previous observations related either to EMT or stemness in breast cancer. We show in silico, that this signature perfectly predicts behavior of tumor cells tested in vitro, and can reflect tumor plasticity. We thus demonstrate for the first time, that breast cancer subtypes are sensitive to either Lapatinib or Midostaurin. The same gene list is not capable of predicting prognosis in most cohorts, except for one that includes patients receiving neo-adjuvant taxene therapy. Significance: CNCL is a robust gene list that can identify both stemness and the EMT state of cell lines and tumors. It can be used to trace tumor cells during the course of phenotypic changes they undergo, that result in altered responses to therapeutic agents. The fact that such a list cannot be used to identify prognosis in most patient cohorts suggests that presence of factors other than stemness and EMT affect mortality.

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Section: Discussioncontrasting

confidence: 99%

A Stemness and EMT Based Gene Expression Signature Identifies Phenotypic Plasticity and is A Predictive but Not Prognostic Biomarker for Breast Cancer

et al. 2020

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“…p < 0.05 was considered as statistically significant. Log-rank tests using all cut-off values (LRMC) for a given dataset were obtained using an in-house, R-based script [23]. Specific statistical analyses are further explained in the figure legends.…”

Section: Statistical Analysesmentioning

confidence: 99%

Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer

et al. 2017

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“…Jin et al [24] found that SEMA5A played a role in cardiac morphogenesis and regeneration. Several studies have also implicated SEMA5A in tumor progression [25-29].…”

Section: Introductionmentioning

confidence: 99%

High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma

et al. 2019

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Background: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. Methods: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Aﬃliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. Results: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical signiﬁcance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). Conclusion: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

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A Combined ULBP2 and SEMA5A Expression Signature as a Prognostic and Predictive Biomarker for Colon Cancer

Cited by 30 publications

References 37 publications

A Stemness and EMT Based Gene Expression Signature Identifies Phenotypic Plasticity and is A Predictive but Not Prognostic Biomarker for Breast Cancer

A Stemness and EMT Based Gene Expression Signature Identifies Phenotypic Plasticity and is A Predictive but Not Prognostic Biomarker for Breast Cancer

Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer

High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma

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