Abstract:Sam68 (Src-associated in mitosis of 68 kD) is a KH domain RNA-binding protein. The expression of Sam68 was correlated with kinds of tumors. Yet, the expression mechanisms and physiological significance of Sam68 in ESCC remains unclear. In this study, we clarified a potential role of Sam68 in the treatment of ESCC. Western blot and immunohistochemistry (IHC) analysis revealed that the protein level of Sam68 was higher in ESCC tumor tissues and cell lines. In addition, IHC stain revealed that Sam68 was positivel… Show more
“…Evidently in a cancer cell, RNA splicing machinery receives aberrant signaling response via Sam68 and results in the generation of oncogenic splicing variant 5–8 . Higher expression of Sam68/KHDRBS1 is shown to play significant role in various cancer cells, such as, colon 9 , prostate 10 , renal 11 , colorectal 12 , breast 13 , esophageal squamous cell carcinoma 6 neuroblastoma 14 bladder cancer 15 renal cell carcinoma 11 , cervical cancer 7 hepatic cancer 16 and non-small lung cancer cells 17 . It is also identified as a prognostic marker in a few cancer tissues 11,15 .…”
Human KHDRBS1/Sam68 is an oncogenic splicing factor involved in signal transduction and pre-mRNA splicing. We explored the molecular mechanism of KHDRBS1 to be a prognostic marker in four different cancers. Within specific cancer, including kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), acute myeloid leukemia (LAML), and ovarian cancer (OV), KHDRBS1 expression is heterogeneous and patient specific. In KIRP and LUAD, higher expression of KHDRBS1 affects the patient survival, but not in LAML and OV. Genome-wide coexpression analysis reveals genes and transcripts which are coexpressed with KHDRBS1 in KIRP and LUAD, form the functional modules which are majorly involved in cancer-specific events. However, in case of LAML and OV, such modules are absent. Irrespective of the higher expression of KHDRBS1, the significant divergence of its biological roles and prognostic value is due to its cancer-specific interaction partners and correlation networks. We conclude that rewiring of KHDRBS1 interactions in cancer is directly associated with patient prognosis.
“…Evidently in a cancer cell, RNA splicing machinery receives aberrant signaling response via Sam68 and results in the generation of oncogenic splicing variant 5–8 . Higher expression of Sam68/KHDRBS1 is shown to play significant role in various cancer cells, such as, colon 9 , prostate 10 , renal 11 , colorectal 12 , breast 13 , esophageal squamous cell carcinoma 6 neuroblastoma 14 bladder cancer 15 renal cell carcinoma 11 , cervical cancer 7 hepatic cancer 16 and non-small lung cancer cells 17 . It is also identified as a prognostic marker in a few cancer tissues 11,15 .…”
Human KHDRBS1/Sam68 is an oncogenic splicing factor involved in signal transduction and pre-mRNA splicing. We explored the molecular mechanism of KHDRBS1 to be a prognostic marker in four different cancers. Within specific cancer, including kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), acute myeloid leukemia (LAML), and ovarian cancer (OV), KHDRBS1 expression is heterogeneous and patient specific. In KIRP and LUAD, higher expression of KHDRBS1 affects the patient survival, but not in LAML and OV. Genome-wide coexpression analysis reveals genes and transcripts which are coexpressed with KHDRBS1 in KIRP and LUAD, form the functional modules which are majorly involved in cancer-specific events. However, in case of LAML and OV, such modules are absent. Irrespective of the higher expression of KHDRBS1, the significant divergence of its biological roles and prognostic value is due to its cancer-specific interaction partners and correlation networks. We conclude that rewiring of KHDRBS1 interactions in cancer is directly associated with patient prognosis.
Background
The aim of this study was to determine the expression and function of heterogeneous nuclear ribonucleoprotein R (HNRNPR) in esophageal carcinoma (ESCA), the correlation between its expression and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerized tomography scan (PET/CT)-related parameters. We also investigated whether 18F-FDG PET/CT can be used to predict the expression of HNRNPR in ESCA.
Methods
We analyzed patients with ESCA who underwent 18F-FDG PET/CT before surgery, and their tissues were stained with HNRNPR IHC. The associated parameters were derived using the 18F-FDG PET imaging data, and the correlation with the IHC score was evaluated. The Oncomine, TCGA, and GEO datasets were used to investigate HNRNPR expression in the pan- and esophageal cancers, as well as its relationship with N6-methyladenosine (m6A) modification and glycolysis. The R software, LinkedOmics, GeneMANIA, and StringOnline tools were used to perform GO/KEGG, GGI, and PPI analyses on the HNRNPR.
Results
HNRNPR is highly expressed in the majority of pan-cancers, including ESCA, and is associated with BMI, weight, and history of reflux in patients with ESCA. HNRNPR is somewhat accurate in predicting the clinical prognosis of ESCA. HNRNPR expression was positively correlated with SUVmax, SUVmean, and TLG in ESCA (p < 0.05). The combination of these three variables provides a strong predictive value for HNRNPR expression in ESCA. GO/KEGG analysis showed that HNRNPR played a role in the regulation of cell cycle, DNA replication, and the Fannie anemia pathway. The analysis of the TCGA and GEO data sets revealed a significant correlation between HNRNPR expression and m6A and glycolysis-related genes. GSEA analysis revealed that HNRNPR was involved in various m6A and glycolysis related-pathways.
Conclusion
HNRNPR overexpression correlates with 18F-FDG uptake in ESCA and may be involved in the regulation of the cell cycle, m6A modification, and cell glycolysis. 18F-FDG PET/CT-related parameters can predict the diagnostic accuracy of HNRNPR expression in ESCA.
“…Sam68 has been identified as an RNA-binding protein and an adaptor recruiting other signaling molecules. 29 Previous studies have demonstrated the significance of Sam68 in carcinogenesis; some of them support the promoting effect of Sam68 on tumor development, 36 , 37 whereas others have shown the tumor suppressive function of Sam68. 40 In this study, we observed an upregulation of Sam68 expression in sacral chordoma compared with normal tissues and found a positive correlation between the expression of Sam68 and cell proliferation index Ki-67, indicating that Sam68 probably promotes the growth of chordomas.…”
Src-associated in mitosis of 68 kDa (Sam68), also known as KHDRBS1 (KH domain-containing, RNA-binding, signal transduction-associated 1), is a member of the signal transduction and activation of RNA family. Previous studies have demonstrated that the aberrant expression of Sam68 is associated with the progression and prognosis of a variety of cancers, but little is known about its expression and role in chordomas, which are rare and aggressive bone neoplasms. In this study, we analyzed 40 tumor tissues and 20 distant normal tissues obtained from 40 patients with sacral chordoma using immunohistochemistry, and observed the expression of Sam68 was significantly upregulated in sacral chordomas compared with normal tissues (P=0.001). A positive correlation between the expression of Sam68 and the cell proliferation index Ki-67 was determined using Spearman’s rank correlation test (γ =0.599, P<0.001). In addition, high expression of Sam68 was significantly associated with surrounding muscle invasion (P<0.001). Moreover, Kaplan–Meier curves showed that patients with overexpressed Sam68 had shorter local recurrence-free survival time (P<0.001). Lastly, multivariate analysis indicated that Sam68 is an independent prognostic factor for the local recurrence-free survival of sacral chordomas (hazard ratio =5.929, 95% CI: 1.092–32.188, P=0.039). Our findings suggest the use of Sam68 as a predictor for the recurrence of sacral chordomas.
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