Prognostic value of ALDH1 and Nestin in advanced cancer: a systematic meta-analysis with trial sequential analysis

Abstract

Background: Novel prognostic markers and therapeutic targets for advanced cancer are urgently needed. This report with trial sequential analysis (TSA) was first conducted to provide robust estimates of the correlation between aldehyde dehydrogenase 1 (ALDH1) and Nestin and clinical outcomes of advanced cancer patients. Methods: Hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), relapse/recurrence-free survival (RFS), and metastasis-free survival (MFS) from multivariable analysis. TSA was performed to control for random errors. Results: A total of 20 studies with 2050 patients (ALDH1: 15 studies with 1557 patients and Nestin: 5 studies with 493 patients) were identified. ALDH1 (HR = 2.28, p < 0.001) and Nestin (HR = 2.39, p < 0.001) were associated with a worse OS, as confirmed by TSA. Nestin positivity was linked to a poor PFS (HR = 2.08, p < 0.001), but ALDH1 was not linked to DFS, RFS, MFS, or PFS, and TSA showed that more studies were needed. Subgroup analysis by tumor type indicated that ALDH1 positivity may be associated with shorter OS in breast, head and neck cancers, but there was no association with colorectal cancer. Subgroup analysis by study source showed that ALDH1 positivity was correlated with a worse OS for Japanese (HR = 1.94, p = 0.002) and European patients (HR = 4.15, p < 0.001), but there was no association for Chinese patients. Subgroup analysis by survival rate showed that ALDH1 positivity correlated with poor OS at ⩾ 5 years (HR = 2.33, p < 0.001) or 10 years (HR = 1.76, p = 0.038). Conclusions: ALDH1 may be more valuable as an effective therapeutic target than Nestin for improving the long-term survival rate of advanced cancer. Additional prospective clinical trials are needed across different cancer types.

CXCR3 from chemokine receptor family correlates with immune infiltration and predicts poor survival in osteosarcoma

“…OS was used as the most common gold standard end point in clinical studies. Because OS is easily measured, the definition is precise, and measurement is reliable and unbiased [19,20]. In this study, an event such as progression, recurrence, second malignant neoplasm, or death was defined as EFS.…”

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

“…The statistical heterogeneity between studies was estimated using the Cochran’s Q statistic [29]. The random-effects model (DerSimonian and Laird method) was used to improve the reliability of the data [30]. When significant heterogeneity was present ( P < 0.1), a sensitivity analysis was performed to evaluate the influence and stability of one study on the results by deleting a single study [31].…”

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

“…Cancer stem cells (CSCs) are a special subpopulation of tumor cells and have the ability and characteristics of self-renewal and multilineage differentiation and proliferation potential, which are related to tumor progression, metastasis, recurrence, prognosis, and drug resistance [6][7][8]. Many CSC-related markers have been identified and reported to be associated with poor prognosis and resistance to therapy in cancer [9,10]. Sex-determining region Y-box 2 (SOX2), a high mobility group (HMG) DNA-binding domain, is mapped to human chromosome 3q26.3-q27 and belongs to a key transcription factor [11].…”