Screening process of publication literatures
The systematically databases search of literatures including initially pertinent publication about the correlation between SNHG15 and cancers in PubMed (n=36), Web of science (n=35), Embase(n=75) and the Cochrane Library(n=0).After originally removing the duplications(n=49),the remained studies(n=97) were browsed for titles and abstracts.72 studies were removed due to irrelvant topics,reviews,case reports,conference abstracts.Next, 25 full-text articles were assessed for eligibility.Among them,nine were removed owing to only focusing on functional exploration of SNHG15,two were excluded for lacking of prognosic data and three articles were precluded due to unclear group number. Ultimately,11 articles containing sufficient datas of both survivals and clinical features were enrolled in our meta-analysis.Figure 1 presented the detailed selection process for qualified publications.
Characteristic description of enrolled studies
Eleven studies with a total of 1087 patients were all performed in China and the published year was from 2016 to 2019.With respect to cancer types,three studies explored lung carcinoma including one lung cancer and two NSCLC, others were respectively gastric cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic ductal adenocarcinoma, breast cancer, papillary thyroid cancer, colorectal cancer, epithelial ovarian cancer.All samples were cancer tissues and adjacent normal tissues and the detection assay was qRT-PCR.Patients were classified as high SNHG15 expression group and low SNHG15 expression group and most studies used median value for cut-off values except one utilizing mean value and one missing. All studies reported overall survival while only two referred to disease-free survival and one mentioned progression-free survival.In terms of HR with 95% CI availability, five studies could obtain from papers directly and the remaining cohorts were retrieved from K-M curves via Engauge Digitiser software.The follow-up time was ranged from 40 to 180 months. The quality of involved studies was assessed by NOS with a range from 6 to 8 scores. The main features of enrolled studies were listed in Table 1.
The association between SNHG15 expression and clinical outcomes
The correlation between SNHG15 expression and clinical features was investigated via calculating the pooled OR with its CI of age, gender, tumor size TNM stage and LNM.The results showed that promoted SNHG15 expression was not significantly related with age(<60 vs ≥60,OR= 0.98, 95% CI: 0.65-1.48,P=0.912, Figure 2(a)),gender(male vs female, OR= 0.95, 95% CI: 0.73-1.25,P= 0.728, Figure 2(b)),tumor size(large vs small, OR= 1.88, 95% CI: 0.91-3.89,P= 0.087, Figure 2(c)).However,significantly association was observed between increased SNHG15 expression and advanced clinical features including TNM stage(III-IV vs I-II, OR= 3.01, 95% CI: 2.15-4.23,P<0.001, Figure 2(d)) and LNM(positive vs negative, OR= 3.20, 95% CI: 2.30-4.45,P<0.001, Figure 2(e)).Four fix-effect models were adopted for the low heterogeneity(0%-35.7%)and only one random-effect model was employed with a significant heterogeneity of 78.4%.The details were characterized in Table 2.
To further demonstrate whether SNHG15 could act as a prognostic predictor of cancers, we explore the association between elevated SNHG15 expression and survival indicators (OS/DFS).All enrolled studies reported the overall survival and forest plot revealed that the pooled HR and 95% CI was 1.95 (1.53-2.49) using fixed-effect model (I2=0%, p=0.778), suggesting promoted SNHG15 expression indicated worse OS (P<0.001,Figure3(a)).Similarly, as shown in Figure3(b),no significant heterogeneity was observed in two studies for DFS(I2=0%, p= 0.822),so the fixed-effect model was employed. The pooled result revealed that increased SNHG15 expression emerged to be dramatically associated with unfavorable DFS (HR= 2.31, 95% CI = 1.48-3.61, P< 0.001, Figure3(b)).Because no obvious heterogeneity was observed in the results so we didn’t performed subgroup analysis. Additionally,we only conducted publication bias for OS due to only two studies reporting DFS.More detailed informations were integrated in Table 2.
Publication bias and sensitivity analysis for prognosis
The pooled HR for OS and DFS was not influenced after removing any study one by one in sensitivity analysis,which meant the reliability and stability of our results(Figure4(a-b)). Furthermore, Begg’s and Egger’s test(P=0.938 and P=0.970) both quantitatively revealed that there was no significant publication bias of OS (Figure4(c-d)).
Validation of the results in GEPIA database
GEPIA database was utilized to further validate our results. In terms of SNHG15 dysregulation, promoted SNHG15 expression was found in colon adenocarcinoma(COAD), lymphoid neoplasm diffuse large B-cell lymphoma(DLBC), kidney renal clear cell carcinoma(KIRC), pancreatic adenocarcinoma(PAAD), rectum adenocarcinoma(READ), testicular germ cell tumors(TGCT), Thymoma(THYM) (Figure 5). Furthermore, increased SNHG15 expression was correlated to unfavourable OS in adrenocortical carcinoma(ACC), kidney renal clear cell carcinoma(KIRC), mesothelioma(MESO), uveal melanoma(UVM) and worse DFS in adrenocortical carcinoma(ACC), prostate adenocarcinoma(PRAD), uveal melanoma(UVM) (log-rank P<0.05) (Figure6-7). These results certified our conclusions in our paper and indicated that SNHG15 could characterized as a novel prognostic biomarker for cancers.