The role of lncRNA CASC2 on prognosis of malignant tumors: a meta-analysis and bioinformatics

Abstract

Background: Cancer susceptibility candidate 2 (CASC2) is characterized as a tumor suppressor, which was first identified to be downregulated in endometrial carcinoma. Accumulating evidence was provided to testify the function of CASC2 in malignant tumors. However, a systematic and quantitative assessment is not available. The present study was designed to evaluate the role of CASC2 in multiple carcinomas through meta-analysis and bioinformatics.

Materials and methods: A systematic assessment of the relationship of CASC2 with tumors was performed by using several computerized databases from inception to December 1, 2017. Pooled HR with 95% CI was calculated to summarize the effect. The data on prognosis of malignant tumors were also downloaded from The Cancer Genome Atlas (TCGA) project, OncoLnc, TANRIC and lncRNAtor database.

Results: A total of 13 studies with 966 cancer patients were pooled in the analysis to evaluate the prognostic value of CASC2 in multiple tumors and the clinical features. The results of the meta-analysis revealed that low expression levels of CASC2 were associated with poor overall survival (OS) (pooled HR=0.39, 95% CI: 0.28-0.53, P<0.0001). CASC2 obviously has a negative correlation with advanced tumor node metastasis (TNM) stage, lymph node metastasis (LNM) and T stage, respectively (P<0.05). There was, however, no significant difference in gender, distant metastasis and high differentiation (P>0.05). In the Kaplan-Meier curves with log-rank analysis, higher expression of CASC2 was positively correlated with longer survival time than patients with a lower level (P<0.05), including kidney renal clear cell carcinoma, brain lower grade glioma, pancreatic adenocarcinoma and sarcoma.

Conclusion: Findings from this meta-analysis suggest that lower expression of CASC2 is associated with poorer prognosis of cancers, as well as advanced TNM, LNM and T stage. Data from the bioinformatics analysis revealed that higher expression of CASC2 was related to longer OS in patients with malignant tumors.

Keywords: CASC2; bioinformatics; malignant tumors; meta-analysis; prognosis.

Figure 1

Flow diagram of the study search and selection process in the meta-analysis.

Figure 2

Forest plot for the association between CASC2 expression and OS. Notes: (A) Unadjusted event rates for OS, (B) adjusted event rates for OS. Abbreviations: ES, effect size; OS, overall survival; CASC2, cancer susceptibility candidate 2.

Figure 3

Forest plot for the association between CASC2 expression and clinicopathological parameters of malignant tumors. Notes: (A) Correlation between gender and CASC2 expression (female vs male), (B) correlation between TNM and CASC2 expression (stage III–IV vs stage I–II), (C) correlation between LNM and CASC2 expression, (D) correlation between DM and CASC2 expression, (E) correlation between T stage and CASC2 expression, (F) correlation between HD and CASC2 expression. Abbreviations: LNM, lymph node metastasis; DM, distant metastasis; TNM, tumor node metastasis.

Figure 4

Funnel plot and Begg’s indicator tests of the publication bias. Notes: (A) Funnel plot for gender, (B) funnel plot for TNM, (C) funnel plot for LNM, (D) Begg’s indicator test for gender, (E) Begg’s indicator test for TNM, (F) Begg’s indicator test for LNM. Abbreviations: LNM, lymph node metastasis; SND, standard normal deviate; TNM, tumor node metastasis.

Figure 5

Sensitivity analyses of studies concerning CASC2. Abbreviation: CASC2, cancer susceptibility candidate 2.

Figure 6

Cox regression results of CASC2 expression in malignant tumors. Abbreviations: BLAC, Bladder urothelial carcinoma; BRCA, Breast invasive carcinoma; CESC, Cervical and endocervical cancers; COAD, Colon adenocarcinoma; ESCA, Esophageal carcinoma; GBM, Glioblastoma multiforme; HNSC, Head and Neck squamous cell carcinoma; KIRC, kidney renal clear cell carcinoma; KIRP, Kidney renal papillary cell carcinoma; LGG, Brain Lower Grade Glioma; LAML, Acute Myeloid Leukemia; LIHC, Liver hepatocellular carcinoma; LUAD, Lung adenocarcinoma; LUSC, Lung squamous cell carcinoma; PAAD, Pancreatic adenocarcinoma; OV, Ovarian serous cystadenocarcinoma; READ, Rectum adenocarcinoma; SARC, Sarcoma; SKCM, Liver hepatocellular carcinoma; STAD, Stomach adenocarcinoma; UCEC, Uterine Corpus Endometrial Carcinoma.

Figure 7

The prognostic significance of CASC2 expression in malignant tumors from TCGA data. Notes: (A) The survival curve of patients with KIRC, (B) the survival curve of patients with LGG, (C) the survival curve of patients with PAAD, (D) the survival curve of patients with SARC. Abbreviations: KIRC, kidney renal clear cell carcinoma; LGG, brain lower grade glioma; PAAD, pancreatic adenocarcinoma; SARC, sarcoma; TCGA, The Cancer Genome Atlas.