RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Objectives: To develop and validate a preoperative CT-based nomogram combined with radiomic and clinical–radiological signatures to distinguish preinvasive lesions from pulmonary invasive lesions. Methods: This was a retrospective, diagnostic study conducted from August 1, 2018, to May 1, 2020, at three centers. Patients with a solitary pulmonary nodule were enrolled in the GDPH center and were divided into two groups (7:3) randomly: development (n = 149) and internal validation (n = 54). The SYSMH center and the ZSLC Center formed an external validation cohort of 170 patients. The least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression analysis were used to feature signatures and transform them into models. Results: The study comprised 373 individuals from three independent centers (female: 225/373, 60.3%; median [IQR] age, 57.0 [48.0–65.0] years). The AUCs for the combined radiomic signature selected from the nodular area and the perinodular area were 0.93, 0.91, and 0.90 in the three cohorts. The nomogram combining the clinical and combined radiomic signatures could accurately predict interstitial invasion in patients with a solitary pulmonary nodule (AUC, 0.94, 0.90, 0.92) in the three cohorts, respectively. The radiomic nomogram outperformed any clinical or radiomic signature in terms of clinical predictive abilities, according to a decision curve analysis and the Akaike information criteria. Conclusions: This study demonstrated that a nomogram constructed by identified clinical–radiological signatures and combined radiomic signatures has the potential to precisely predict pathology invasiveness. Key Points: • The radiomic signature from the perinodular area has the potential to predict pathology invasiveness of the solitary pulmonary nodule. • The new radiomic nomogram was useful in clinical decision-making associated with personalized surgical intervention and therapeutic regimen selection in patients with early-stage non-small-cell lung cancer.

Purpose: The present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and Methods: In this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.Results: One hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.Conclusion: Our results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Background: Mouse double minute 2 (MDM2) contributes to cancer metastasis and epithelial–mesenchymal transition (EMT). This study aimed to investigate small mothers against decapentaplegic (Smad) signaling in MDM2-mediated EMT in lung adenocarcinoma (LAC). Materials and methods: Expression patterns of MDM2 in LAC tissues, adjacent tissues, and cell lines (BEAS-2B, PC9, H1975, and A549) were detected. We then overexpressed MDM2 in PC9 cells and knocked it down in H1975 cells. To explore whether MDM2 activates EMT through the Smad2/3 signaling pathway, Smad2 and Smad3 were also silenced by siRNA in H1975 cells. Male BALB/c nude mice were used in in vivo model to validate the effects of MDM2 on LAC cells. Results: MDM2 was significantly upregulated in LAC tissues compared with adjacent tissues. The expression of MDM2 was relatively higher in PC9 cells and relatively lower in H1975 cells compared with A549 cells. Overexpression of MDM2 significantly increased cell proliferation, migration, and invasion in LAC cells, while inhibiting apoptosis in PC9 cells. On the contrary, silencing of MDM2 significantly inhibited the expression of EMT-related genes N-cadherin and vimentin, while promoting the expression of E-cadherin and β-catenin. In vivo, MDM2 knockdown inhibited tumor growth. In addition, the expression of Smad2/3 was correlated with MDM2 in H1975 cells transfected with Smad2 and Smad3 siRNAs, which inhibited EMT progress. Conclusion: MDM2 can activate the Smad2/3 signaling pathway, which promotes the proliferation and EMT progress of LAC cells.

Background: Exploring the cancer risks of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARDs) can help detect, evaluate, and treat malignancies at an early stage for these patients. Thus, a comprehensive analysis was conducted to determine the cancer risk of RA patients using different types of DMARDs and analyze their relationship with tumor mutational burdens (TMBs) reflecting immunogenicity.Methods: A thorough search of PubMed, EMBASE, Web of Science, and Medline was conducted up to 20 August 2022. Standardized incidence ratios (SIRs) were constructed with a random-effect model to determine risks for different types of malignancies in comparison with the general population. We also analyzed the correlation between SIRs and TMBs using linear regression (LR).Results: From a total of 22 studies, data on 371,311 RA patients receiving different types of DMARDs, 36 kinds of malignancies, and four regions were available. Overall cancer risks were 1.15 (SIR 1.15; 1.09–1.22; p < 0.001) and 0.91 (SIR 0.91; 0.72–1.14; p = 0.402) in RA populations using conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs), respectively. RA patients taking csDMARDs displayed a 1.77-fold lung cancer risk (SIR 1.77; 1.50–2.09; p < 0.001), a 2.15-fold lymphoma risk (SIR 2.15; 1.78–2.59; p < 0.001), and a 1.72-fold melanoma risk (SIR 1.72; 1.26–2.36; p = 0.001). Correlation coefficients between TMBs and SIRs were 0.22 and 0.29 from those taking csDMARDs and bDMARDs, respectively.Conclusion: We demonstrated a cancer risk spectrum of RA populations using DMARDs. Additionally, TMBs were not associated with elevated cancer risks in RA patients following immunosuppressive therapy, which confirmed that iatrogenic immunosuppression might not increase cancer risks in patients with RA.Interpretation: Changes were similar in cancer risk after different immunosuppressive treatments, and there was a lack of correlation between SIRs and TMBs. These suggest that we should look for causes of increased risks from the RA disease itself, rather than using different types of DMARDs.