Wilms’ tumor 1-associating protein (WTAP) is required for N⁶-methyladenosine (m⁶A) RNA methylation modifications, which regulate biological processes such as RNA splicing, cell proliferation, cell cycle, and embryonic development. m⁶A is the predominant form of mRNA modification in eukaryotes. WTAP exerts m⁶A modification by binding to methyltransferase-like 3 (METTL3) in the nucleus to form the METTL3-methyltransferase-like 14 (METTL14)-WTAP (MMW) complex, a core component of the methyltransferase complex (MTC), and localizing to the nuclear patches. Studies have demonstrated that WTAP plays a critical role in various cancers, both dependent and independent of its role in m⁶A modification of methyltransferases. Here, we describe the recent findings on the structural features of WTAP, the mechanisms by which WTAP regulates the biological functions, and the molecular mechanisms of its functions in various cancers. By summarizing the latest WTAP research, we expect to provide new directions and insights for oncology research and discover new targets for cancer treatment.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death worldwide. Early diagnosis is essential for improvements of prognosis and survival of the patients. Currently, there is no effective biomarker available in clinical settings for early detection of lung cancer. Altered expressions in many cancer types including NSCLC and stable existence in plasma make microRNAs (miRNAs) a group of potentially useful biomarkers for clinical assessments of patients with NSCLC. To evaluate the potential values of miRNAs as blood-based biomarkers for early diagnosis and prognosis in NSCLC patients. Peripheral blood samples from healthy volunteers and early-staged NSCLC patients before and after surgery were collected, and plasma was separated. Expression of ten miRNAs in the plasma and tumor sections of the patients was detected by quantitative real-time polymerase chain reaction. MiRNA (miR)-486 and miR-150 were found to significantly distinguish lung cancer patients from healthy volunteers. Area under curve of miR-486 and miR-150 were 0.926 (sensitivity, 0.909; specificity, 0.818) and 0.752 (sensitivity, 0.818; specificity, 0.818), respectively. In response to therapy, patients with down-regulated miR-486 expression showed prolonged recurrence-free survival than those with un-reduced miR-486 expression (median, unreached vs. 19 months; hazard ratio, 0.1053; 95% confidence interval, 0.01045 to 1.060; P=0.056). The results suggest that miR-486 and miR-150 could be potential blood-based biomarkers for early diagnosis of NSCLC. Monitoring change of miR-486 expression in plasma might be an effective and non-invasive method for recurrence prediction of early-staged NSCLC patients.

HIF-α may play an important role in the process of tumorigenesis as well as tumor progression. Although a number of investigations have established the significance of HIF-1α in several human tumors, there is still little information available on the clinical significance of HIF-2α expression in non-small cell lung cancer (NSCLC). In present study, immunohistologic expression of HIF-1α/ HIF-2α was studied in a tissue microarray of 140 Stage I-III NSCLCs and correlated with clinicopathologic parameters and clinical outcome. We found that HIF-1α/ HIF-2α showed a cytoplasmic pattern of expression in tumor cells while normal lung components showed negative or weak cytoplasmic staining. High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases respectively. There was no direct correlation between HIF-1α and HIF-2α expression (p = 0.200). The high HIF-2α expression was associated with histology (squamous cell carcinoma vs. adenocarcinomas) in these patients (p = 0.001). Patients in advanced tumor stage had frequent high expression of HIF-2α (p = 0.007), and the similar high expression was also observed in advanced T or N stage (p = 0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (p = 0.084), which showed a higher expression in early tumor stage. Univariate analysis of the overall survival demonstrates that HIF-2α expression but not HIF-1α was related to poor outcome (p = 0.005) and it retained significance in multivariate analysis (p = 0.046). In conclusion, HIF-2α expression was related to tumor size, lymph node metastasis, tumor stage and histology. We also found a positive prognostic value of HIF-2α protein expression. HIF-2α might serve as a potential prognosis biomarker in evaluating progression and prognosis of NSCLC. We believe that our study will be of great benefit to the clinical treatment and prognostic evaluation of NSCLC.

To compare dual energy CT iodine imaging and standardized iodine concentration before and after chemoradiotherapy (CRT) for esophageal cancer and evaluate the efficacy of CRT for EC by examining DECT iodine maps and standard CT values. The clinical data of 45 patients confirmed by pathology with newly diagnosed esophageal cancer who underwent concurrent CRT from February 2012 to January 2017 in our department of radiology were collected. All patients underwent dual-source dual-energy CT (DECT) before and after CRT. Normalized iodine concentration (NIC) and normalized CT (NCT) corresponding to the overall cancer lesion and its maximum cross-sectional area were observed and compared. Additionally, 30 healthy individuals were compared as control group. After treatment, the patients were divided into two groups according to RECIST1.1: treatment effective group and ineffective group. There were 33 patients (CR 9, PR 24) in the effective group and 12 patients (SD 12, PD 0) in the ineffective group. There was no significant difference in the NIC-A, NIC-V, NCT-A and NCT-A indexes between the effective group (B group) and the ineffective group (C group) before treatment (P > 0.05). After the treatment, the above-mentioned indexes in the effective group of patients were significantly lower than before treatment, and compared with the ineffective group, the NIC-A, NIC-V, NCT-A and NCT-V values of the effective group were significantly lower than those of ineffective group (P < 0.05). After treatment, the NIC-V and NCT-V in the ineffective group were lower than before treatment, and the difference was statistically significant (P < 0.05). However, their NIC-A and NCT-A were not statistically different from those before treatment (P > 0.05). Using DECT iodine map, the changes of NIC and NIC before and after CRT in patients with esophageal cancer can evaluate the effect of CRT, and does not increase the radiation dose, so it is suitable for clinical use.

Purpose: The role of RNA N6-methyladenosine (m⁶A) modification in the progression of multiple tumours and the tumour microenvironment (TME) has been progressively demonstrated and promises a new direction for tumour therapy. However, there have been no reports on systematic analyses of RNA m⁶A modification in TME in non-small cell lung cancer (NSCLC). Patients and Methods: In this study, we used unsupervised cluster analysis to identify three m⁶A modification patterns of 28 m⁶A regulators and three m⁶A gene signature subgroups of commonly differentially expressed genes (co-DEGs) in the three m⁶A modification patterns. Quantifying these subtypes using the ssGSEA and ESTIMATE algorithms to characterise the tumour immune microenvironment (TIME) in NSCLC. Based on the principal component analysis (PCA), we used co-DEGs to construct m⁶A scores to analyse the characteristics of m⁶A modifications in individual patients and assessed the practical clinical utility of m⁶A scores using a nomogram for survival prediction. Results: A total of 28 m⁶A regulators in 1210 NSCLC samples were mainly enriched in RNA modification and metabolic biological processes. The three following m⁶A modification patterns were identified based on the role of the 28 m⁶A regulators in TME: immune inflammation, immune evasion and immune desert. The m⁶A scores calculated based on co-DEGs in these modification patterns were significantly positively correlated with immune infiltration and significantly negatively correlated with tumour mutational burden (TMB). Survival was significantly better in the high-m⁶A-score group than in the low-m⁶A-score group, and the m⁶A score could be used as an independent favourable prognostic factor. In addition, assessment of both immune checkpoint inhibitors (ICIs) and immunophenoscore (IPS) revealed a better immunotherapeutic effect in the high-m⁶A-score group. Conclusion: The modification characteristics of 28 m⁶A regulators in the TIME of NSCLC were analysed from a comprehensive to an individual basis, which may facilitate the development of more effective clinical immunotherapeutic strategies. Graphical Abstract: