Prognostic Value of CD44 and Its Isoforms in Advanced Cancer: A Systematic Meta-Analysis With Trial Sequential Analysis

Han, Susu; Huang, Tao; Li, Wen; Wang, Xiyu; Wu, Xing; Liu, Shanshan; Yang, Wei; Shi, Qi; Li, Hongjia; Hou, Fenggang

doi:10.3389/fonc.2019.00039

Cited by 24 publications

(16 citation statements)

References 66 publications

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“…In this study, although high PKM2 mRNA and protein levels were associated with both reduced mPFS and mOS, high CD44 protein levels were associated only with reduced mOS. Similarly, in recent systematic analysis of 1201 patients with advanced carcinomas selected from fifteen studies, CD44 expression was linked only to worse OS and not to DFS, RFS, or PFS [43]. Nevertheless, the CD44 histoscore in our study, that is the continuous variable, not only was negatively associated with both mPFS and mOS but also was an independent prognostic factor for mOS in contrast with the PKM2 histoscore.…”

Section: Discussionsupporting

confidence: 60%

Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Papadaki

Manolakou

Lagoudaki

et al. 2020

Cancers

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CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.

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Section: Discussionsupporting

confidence: 60%

Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Papadaki

Manolakou

Lagoudaki

et al. 2020

Cancers

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“…CSCs contribute to tumor metastasis and prognosis and therapeutic resistance [45,46]. CSCs may offer new promising therapeutic targets of treatment modalities applicable to human various cancers [47,48].…”

Section: Discussionmentioning

confidence: 99%

Clinical and Survival Impact of Sex-Determining Region Y-Box 2 in Colorectal Cancer: An Integrated Analysis of the Immunohistochemical Study and Bioinformatics Analysis

Song

Hao

et al. 2020

Journal of Oncology

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Transcription factor sex-determining region Y-box 2 (SOX2) involves in the maintenance of cancer stem cells. However, the role of SOX2 in colorectal cancer (CRC) remains unclear. This study was conducted to investigate the effect of SOX2 on CRC. Studies were searched using electronic databases. The combined odds ratios (ORs) or hazard ratios (HRs: multivariate Cox survival analysis) with their 95% confidence intervals (CIs) were calculated. The Cancer Genome Atlas (TCGA) and GEO datasets were further applied to validate the survival effect. The functional analysis of SOX2 was investigated. In this work, 13 studies including 2337 patients were identified, and validation data were enrolled from TCGA and GEO datasets. SOX2 expression was not significantly related to age, gender, microsatellite instability (MSI) status, clinical stage, histological grade, tumor size, pT-stage, lymph node metastasis, distal metastasis, and cancer-specific survival (CSS) but was correlated with worse overall survival (OS: n = 536 patients) (P<0.05). Furthermore, TCGA data demonstrated similar results, with no significant correlation between SOX2 and pathological characteristics. Further validation data (OS: n = 1408 and disease-free survival (DFS): n = 1367) showed that SOX2 expression was correlated with worse OS (HR = 1.35, 95% CI: 1.11–1.65, P=0.004) and DFS (HR = 1.30, 95% CI: 1.04–1.62, P=0.02). The functional analyses showed that SOX2 involved in cell-cell junction, focal adhesion, extracellular matrix- (ECM-) receptor interaction, and MAP kinase activity. Our findings suggest that SOX2 expression may be correlated with the worse prognosis of CRC.

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“…Cancer stem cells (CSCs) are a small group of cells within tumors and are responsible for self-renewal, uncontrolled differentiation, and tumorigenicity [6, 7]. CSCs contribute to cancer development, progression, and metastasis [8–10].…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis and The Cancer Genome Atlas data of prostate cancer risk and prognosis using epithelial cell adhesion molecule (EpCAM) expression

Gao

et al. 2019

BMC Urol

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Background: Epithelial cell adhesion molecule (EpCAM) expression has been reported in many types of cancer, including prostate cancer (PCa). However, the role of EpCAM expression remains inconsistent. We conducted a meta-analysis to assess the clinicopathological and prognostic significance of EpCAM expression in PCa. Methods: Publications were searched online using electronic databases. The available data were obtained from The Cancer Genome Atlas (TCGA). The odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (CIs) were calculated. Results: We identified seven studies in which immunohistochemistry was used and that included 871 prostatic tissue samples. EpCAM expression was significantly higher in PCa samples than in benign and normal tissue samples (OR = 77.93, P = 0.002; OR = 161.61, P < 0.001; respectively). No correlation of EpCAM overexpression with pT stage and lymph node metastasis was observed; however, EpCAM overexpression showed a significant correlation with Gleason score (OR = 0.48, P = 0.012) and bone metastasis (OR = 145.80, P < 0.001). Furthermore, TCGA data showed that EpCAM overexpression was not closely correlated with age, pT stage, lymph node metastasis, number of lymph node, prostate-specific antigen level, Gleason score, biochemical recurrence, and overall survival. Based on multivariate Cox proportional-hazards regression analysis, a significant correlation was observed between EpCAM overexpression and 5-year worse biochemical recurrence free-survival. Conclusions: EpCAM overexpression may be correlated with the development of bone metastasis and worse biochemical recurrence free-survival of PCa. Further studies are needed to verify these findings.

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Prognostic Value of CD44 and Its Isoforms in Advanced Cancer: A Systematic Meta-Analysis With Trial Sequential Analysis

Cited by 24 publications

References 66 publications

Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Clinical and Survival Impact of Sex-Determining Region Y-Box 2 in Colorectal Cancer: An Integrated Analysis of the Immunohistochemical Study and Bioinformatics Analysis

A meta-analysis and The Cancer Genome Atlas data of prostate cancer risk and prognosis using epithelial cell adhesion molecule (EpCAM) expression

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