Collective evidence has indicated that lncRNA AWPPH is closely related to cancer. Initially, lncRNA AWPPH was identified as an overexpressed oncogene in hepatocellular carcinoma [11]. Its overexpression is associated with tumor size, clinical stage, and poor prognosis in patients with hepatocellular carcinoma [21]. Currently, lncRNA AWPPH has been confirmed as a dysregulated oncogene in other several malignancies, such as GC [21], CRC [31], NSCLC [12]. Moreover, the silence of AWPPH significantly suppressed cell proliferation, migration, and invasion in a variety of human cancers. It has drawn great attention as carcinogenic lncRNA in many kinds of cancers. Many researchers focused on the clinical potential value in predicting cancer prognosis. However, inconsistency regarding the predictive value of lncRNA AWPPH in some prognostic parameters, e.g., TNM stage, LNM, and DM, arise from a wide range of studies due to heterogeneity.
In the present meta-analysis, we found that patients with elevated AWPPH expression tended to have poorer OS in cancer patients. Namely, high lncRNA AWPPH expression may serve as an independent predictive factor for the prognosis of cancer patients. Meanwhile, this study also revealed that AWPPH overexpression significantly associated with more advanced TNM stage, higher risk of LNM and MVI, and bigger tumor size. To sum up, our finding suggested that lncRNA could serve as a potential independent prognostic factor for predicting clinical outcomes for cancer patients. However, the underlying molecular mechanism of aberrant AWPPH expression correlated with poor clinical prognosis remains elusive.
Many studies have investigated the functional mechanism of lncRNA AWPPH on tumorigenesis and tumor progression in various cancers (Fig. 8). Previous stduy reported that AWPPH regulates cell proliferation and cell cycle via modulating MDM2/p53 signaling in ESCC [32]. AWPPH acted/functioned as an oncogene to interact with YBX1 to activate the expression of SNAIL1 and PI3K/AKT pathway in the HCC [32]. Wnt/β-catenin signal pathway has been revealed to be involved in the regulation of cell proliferation, migration, and invasion in certain cancers [33, 34]. It was reported that lncRNA AWPPH could promote the proliferation, migration, and invasion of breast cancer, ovarian carcinoma, and NSCLC by activating the Wnt/β-catenin signal pathway [12, 29, 35]. Moreover, several important pathways were conformed to be modulated by AWPPH in cancers, including MDM2-p53 pathway esophageal squamous cell carcinoma [32], and MEK/ERK pathway in HCC [21]. Furthermore, AWPPH could inhibit colon cancer cell proliferation by downregulating GLUT-1 [36] and cancers by upregulating TGF-β1 [28, 37, 38]. Liu et al. demonstrated that AWPPH contributes to cisplatin resistance by inducing the expression of CDK1 and GTSE5 (cell cycle-associated factors), and suppressed the expression of CCNC and BIRC5 (cell apoptosis-associated factors), providing a brand new insight for the cisplatin resistance of gastric cancer NSCLC [39].
In addition, growing evidence has demonstrated that AWPPH functions as competitive endogenous RNA (ceRNA) to regulate miRNAs, and plays a key role in the initiation, development, and chemoresistance of cancer. In gastric cancer, Bu et al. demonstrated that AWPPH promotes cell proliferation and tumorigenesis by regulating miR-497/NTRK3 axis [22]. Recently, miR-128-3p was found to be a target of AWPPH in ovarian cancer by Zhu et al. [13]. In NSCLC, Wu et al. also demonstrated that AWPPH could function as an oncogenic lncRNA by regulating miR-204/CDK6 axis [25]. Furthermore, AWPPH functioned as a ceRNA to promote malignant progression of human cancers through competitive sponging of miR-93-3p in osteosarcoma [27], miR-802 in melanoma [40], miR-206 in CRC [17], miR-1224-5p in glioblastoma [41], and miR-513a-5p in CCRCC [42].
Several limitations existed in this meta-analysis owing to the discrete data across these clinical studies. First, all included studies were performed in China, which might limit the applicability of our results for other ethnic population. Second, the cut-off values are different among the included articles. Third, some of the HRs were calculated by reconstructing survival curves, which might result in a calculation bias. Finally, only studies published in English or Chinese were obtained in this meta-analysis, and the data collection may be incomplete.