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Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis. In this study, we conducted genome-wide gene expression association analyses in pediatric B-ALL cohorts to discover expression associated genes and pathways, which is followed by the bioinformatics analyses to investigate the prognostic role of PIP4K2A and its related genes in multiple cancer types. 214 candidates were identified to be significantly associated with PIP4K2A expression in ALL patients, with known cancer-related genes rankings the top (e.g., RAC2, RBL2, and TFDP1). These candidates do not only tend to be clustered in the same types of leukemia, but can also separate the patients into novel molecular subtypes. PIP4K2A is noticed to be frequently overexpressed in multiple other types of leukemia and solid cancers from cancer cohorts including TCGA, and associated with its candidates in subtype-specific and cancer-specific manners. Interestingly, the association status varied in tumors compared to their matched normal tissues. Moreover, PIP4K2A and its related candidates exhibit stage-independent prognostic effects in multiple cancers, mostly with its lower expression significantly associated with longer overall survival (p < 0.05). Our findings reveal the transcriptional regulatory network of PIP4K2A in leukemia, and suggest its potentially important role on molecular subtypes of multiple cancers and subsequent treatment outcomes.

tRNA-derived small non-coding RNAs (tsncRNAs), a class of newly defined small non-coding RNA, have been considered to be involved in various cellular biological processes through regulating gene expression at both transcriptional and post-transcriptional level. However, the presence of circulating tsncRNAs and their diagnostic potential is largely unclear. In this study, we investigate the serum-derived public transcriptome data from ovarian tumor patients and non-cancer controls, and find that circulating tsncRNAs cover a high proportion of total small RNA and are non-random degradation products in serum (ranging from 2.5–29.4%), which are enriched in several specific types of related tRNA (e.g., Gly-tRNA). Particularly, four tsncRNAs are differentially expressed in serum from cancer patients compared to those from healthy controls, and can predict abnormal cell proliferation with high accuracy. Our results reveal the ubiquitous presence of circulating tsncRNAs in serum, and diagnostic potential of specific tsncRNAs for ovarian tumor. Electronic supplementary material The online version of this article (10.1186/s12943-018-0910-1) contains supplementary material, which is available to authorized users.