Radiogenomic association between the T2-FLAIR mismatch sign and IDH mutation status in adult patients with lower-grade gliomas: an updated systematic review and meta-analysis.

OBJECTIVES: To reveal a radiogenomic correlation between the presence of the T2-fluid-attenuated inversion recovery resection (T2-FLAIR) mismatch sign on MR images and isocitrate dehydrogenase (IDH) mutation status in adult patients with lower-grade gliomas (LGGs). METHODS: A web-based systemic search for eligible literature up to April 13, 2021, was conducted on PubMed, Embase, and the Cochrane Library databases by two independent reviewers. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We included studies evaluating the accuracy of the T2-FLAIR mismatch sign in diagnosing the IDH mutation in adult patients with LGGs. The T2-FLAIR mismatch sign was defined as a T2-hyperintense lesion that is hypointense on FLAIR except for a hyperintense rim. RESULTS: Fourteen studies (n = 1986) were finally identified. The mean age of patients in the included studies ranged from 38.5 to 56 years. The pooled area under the curve (AUC), sensitivity, and specificity were obtained for each molecular profile: IDHmut-Codel: 0.46 (95% confidence interval [CI]: 0.42-0.50), 1% (95%CI: 0-7%), and 69% (95%CI: 62-75%), respectively; IDHmut-Noncodel: 0.75 (95%CI: 0.71-0.79), 42% (95%CI: 34-50%), and 99% (95%CI: 96-100%), respectively; IDH-Mutation regardless of 1p/19q codeletion status: 0.77 (95%CI: 0.73-0.80), 29% (95%CI: 21-40%), and 99% (95%CI: 92-100%), respectively. CONCLUSIONS: The T2-FLAIR mismatch sign was an insensitive but highly specific marker for IDHmut-Noncodel and IDH-Mutation LGGs, whereas it was not a useful marker for IDHmut-Codel LGGs. The findings might identify the T2-FLAIR mismatch sign as a non-invasive imaging biomarker for the selection of patients with IDH-mutant LGGs. KEY POINTS: • The T2-FLAIR mismatch sign was not a sensitive sign for IDH mutation in LGGs. • The T2-FLAIR mismatch sign was related to IDHmut-Noncodel with a specificity of 99%. • The pooled specificity (69%) of the T2-FLAIR mismatch sign for IDHmut-Codel was low.

Proteome-Wide Analysis Reveals TFEB Targets for Establishment of a Prognostic Signature to Predict Clinical Outcomes of Colorectal Cancer.

Dephosphorylation of transcription factor EB (TFEB) at Ser142 and Ser138 determines its nuclear localization and transcriptional activity. The link between TFEB-associated genes and colorectal cancer (CRC) progression and prognosis remains unclear. To systematically identify the targets of TFEB, we performed data-independent acquisition (DIA)-based quantitative proteomics to compare global protein changes in wild-type (WT) DLD1 cells and TFEBWT- or TFEBS142A/S138A (activated status)-expressing DLD1 cells. A total of 6048 proteins were identified and quantified in three independent experiments. The differentially expressed proteins in TFEBS142A/S138A versus TFEBWT and TFEBWT versus control groups were compared, and 60 proteins were identified as products of TFEB transcriptional regulation. These proteins were significantly associated with vesicular endocytic trafficking, the HIF-1 signaling pathway, and metabolic processes. Furthermore, we generated a TFEB-associated gene signature using a univariate and LASSO Cox regression model to screen robust prognostic markers. An eight-gene signature (PLSCR3, SERPINA1, ATP6V1C2, TIMP1, SORT1, MAP2, KDM4B, and DDAH2) was identified. According to the signature, patients were assigned to high-risk and low-risk groups. Higher risk scores meant worse overall survival and higher epithelial-mesenchymal transition (EMT) scores. Additionally, as per the clinicopathological parameters and gene signature, a nomogram was constructed that was utilized to enhance the quantification capacity in risk assessment for individual patients. This research shows that TFEB directly mediates network effects in CRC, and the identified TFEB gene signature-based model may provide important information for the clinical judgment of prognosis.