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Review
. 2020 Nov 27;40(11):BSR20190372.
doi: 10.1042/BSR20190372.

The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

Yongping Zhang #  1 , Chaojie Liang #  1 , Yu Zhang  1 , Zhinmin Wang  1 , Ruihuan Li  1 , Zhigang Wei  1 , Jiansheng Guo  1
Affiliations
Review

The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

Yongping Zhang et al. Biosci Rep. .

Abstract

Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients.

Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers.

Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis.

Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

Keywords: FOXD2-AS1; Neoplasm; long non-coding RNA; meta-analysis; prognosis.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Flow diagram of the meta-analysis
Figure 2
Figure 2. The relationship between FOXD2-AS1 expression and OS rate
Figure 3
Figure 3. Subgroup analysis of OS
Subgroup analysis by (A) source and (B) region.
Figure 4
Figure 4. Subgroup analysis of OS
Subgroup analysis by (A) tumor type and (B) sample size.
Figure 5
Figure 5. Forest plot of DFS
Figure 6
Figure 6. Begg’s publication bias plots and sensitivity analysis of studies evaluating the relationship between FOXD2-AS1 expression and survival rate
(A) Begg’s publication bias of OS. (B) Sensitivity analysis of OS. (C) Begg’s publication bias of DFS. (D) Sensitivity analysis of DFS.
Figure 7
Figure 7. The expression of FOXD2-AS1 in TCGA dataset
(A) FOXD2-AS1 expression in CHOL, COAD, DLBC, ESCA, PAAD, READ, SKCM, STAD, and THYM, which was analyzed by one-way ANOVA. ‘*’ means log2FC value > 1 and P-value <0.01. (B) OS rate of FOXD2-AS1 expression in TCGA (n=9502, Log-rank P<0.01). (C) DFS rate of FOXD2-AS1 in TCGA cohort (n=9502, Log-rank P<0.01). Red boxes indicate cancer, and gray boxes indicate normal.
Figure 8
Figure 8. Validation of FOXD2-AS1 expression in TCGA cohort
(A) OS in GI cancer patients (n=926, Log-rank P=0.013). (B) DFS in GI tumors (n=926, Log-rank P=0.045). (C) OS in hepatobiliary and pancreatic cancer patients (n=578, Log-rank P=0.0014). (D) DFS in hepatobiliary and pancreatic cancer patients (n=578, Log-rank P=0.06). (E) OS in respiratory cancer patients (n=957, Log-rank P=0.23). (F) DFS in respiratory cancer patients (n=957, Log-rank P=0.021). (G) OS in urinary cancer patients (n=1964, Log-rank <0.001). (H) DFS in urinary cancer patients (n=1964, Log-rank =0.001). (I) OS in female reproductive cancer patients (n=1703, Log-rank P=0.0011). (J) DFS in female reproductive cancer patients (n=1703, Log-rank P<0.001). (K) OS in head and neck cancer patients (n=1024, Log-rank P<0.001). (L) DFS in head and neck cancer patients (n=1024, Log-rank P<0.001).
Figure 9
Figure 9. Meta-analysis evaluation of the association between FOXD2-AS1 expression and clinicopathological characteristics
(A) Gender; (B) age; (C) tumor size; (D) differentiation; (E) lymph node metastasis; and (F) TNM stage.
See this image and copyright information in PMC

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