Details of included study
As shown in Figure 1, after strict selection by two authors, 23 studies of 2263 cancer patients were included in this study. The detailed characteristics of the 23 studies were summarized in Table1. Those studies were published from 2015 to 2020, with average sample size about 103. The included 2263 patients all come from China. 16 types of tumors were included in this study, which contains pancreatic adenocarcinoma (PAAD) [10], hepatocellular carcinoma (HCC) [11, 18], melanoma [12], esophageal squamous cell carcinoma (ESCC) [13, 19], hepatoblastoma (HB) [20], cholangiocarcinoma (CCA) [14], papillary thyroid carcinoma (PTC) [21], prostate cancer (PCa) [22], clear cell renal cell carcinoma (ccRCC) [15], colorectal cancer (CRC) [16, 23, 24], bladder cancer [25, 26], nasopharyngeal carcinoma (NPC) [27], gastric cancer (GC) [28], epithelial ovarian cancer (EOC) [29], non-small cell lung cancer (NSCLC) [30], glioma [31]. ZFAS1 expression in tumor tissues were all detected by qRT-PCR. The NOS score of included studies are all ≥6,which means they are all high quality studies. Additionally, the study of Shi et al. provided two independent cohorts of patients, so we didn’t merge the data together, but named the data from primary cohort as Shi HT and the validation cohort as Shi HT-1.
ZFAS1 expression and OS
In this part, 16 studies of 1637 patients were included. Among them, 5 studies directly provided HR and 95%CI, and the survival data from the other 11 studies were indirectly extracted from survive curve. The results revealed that patients with high ZFAS1 expression underwent poor OS (OR=1.80, 95%CI: 1.50-2.10, P≤0.001, Figure 2). It’s found that many different characteristics were existed among the study of OS, therefore, to exclude potential bias, subgroup analysis on the basis of HR methods, sample size, follow-up month and tumor type indicate that high ZFAS1 expression was correlated to poor OS in the above 8 subgroups (Figure 3), which indicates there exists no potential bias in study about OS. Additionally, sensitivity analysis and Begg’s test further confirms the robustness of this results (Figure 4).
ZFAS1 expression and clinical characteristics
OR and 95%CI was applied to evaluate the relationship between ZFAS1 expression and various clinical characteristics. As manifested in Figure 5, the results demonstrated that high ZFAS1 expression was related to high tumor stage (HTS) (OR=2.99, 95%CI: 1.97-4.54, P≤0.001, Figure 5a), larger tumor size (LTS) (OR=1.54, 95%CI: 1.05-2.24, P≤0.001, Figure 5b), lymph node metastasis (LNM) (OR=2.67, 95%CI: 1.73-4.14, P≤0.001, Figure 5c), poor histologic grade (PHG) (OR=1.57, 95%CI: 1.09-2.26, P=0.015, Figure 5d), distant metastasis (DM) (OR=3.45, 95%CI: 1.61-7.39, P=0.001, Figure S1a), but not to age (OR=1.06, 95%CI: 0.89-1.26, P=0.499, Figure S1b) and gender (OR=1.13, 95%CI: 0.94-1.36, P=0.209, Figure S1c).
And Begg’s test in Figure 6 manifested that there exists no publication bias in the studies of LNM (Pr > |z| =0.322), DM (Pr > |z| =0.060), HTS (Pr> |z| = 0.173), LTS (Pr > |z| =1.000), PHG (Pr > |z| =0.381).
CeRNA network
Growing studies have found out that CeRNA network plays a significant role in the regulation of lncRNA to cancer. To explore the potential mechanism of ZFAS1 in cancer development, the CeRNA network centered on ZFAS1 was constructed. As shown in Figure 6, this CeRNA network which contains 95 nodes and 103 edges manifested lots of ZFAS1/miRNA/mRNA axis that may participate in the regulation of occurrence and development of cancer. GO and KEGG analysis indicated the biological functions and pathway the targeted mRNAs may involve in. Those results above together provide meaningful clues for future mechanism research of ZFAS1 in cancer.