Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs.

Background: Genetic factors play an important role in colorectal cancer (CRC) risk, yet the prevalence and spectrum of germline cancer susceptibility gene mutations among unselected Chinese CRC patients is largely undetermined. Methods: We performed next-generation sequencing with a 73-genes panel and analyzed the prevalence and spectrum of germline mutations in 618 unselected Chinese CRC patients. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations. Clinical characteristics were assessed by age and mutation status. Protein expressions and interactions of MLH1 missense variants were evaluated by western blot and co- immunoprecipitation. Results: Overall, 112 (18.1%) of 618 unselected Chinese CRC patients were found to carry at least one pathogenic or likely pathogenic variant (totaling 97 variants), including 70 (11.3%) Lynch syndrome (LS) mutation carriers and 42 (6.8%) non-LS mutation carriers. LS mutation carriers were significantly younger at CRC diagnosis and were more likely to have right-sided, poorly differentiated, early stage, high-frequency microsatellite instability (MSI-H) or dMMR CRC and a family history of cancer compared with noncarriers. Non-LS mutation carriers were more likely to be proficient mismatch repair (pMMR) than noncarriers (p=0.039). We found four clinical variables (gender, tumor histological stage, cancer stage and mutation status) that showed significant differences between patients younger and older than 50 years old. Higher mutation rates were found in patients under 50 years old (p=0.017). Thirty-three novel variants were discovered and evaluated as pathogenic mutations by our study. Conclusion: Given the high frequency and wide spectrum of mutations, genetic testing with a multigene panel should be considered for all Chinese CRC patients under 50 years old and is also needed to determine whether a gene is associated with CRC susceptibility and to promote clinical translation.

Background This study aimed to explore the prognostic value of tumor mutational burden (TMB) combined with smoking status in advanced non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitor therapy (anti PD-1/PD-L1 therapy) combined with chemotherapy or anti-angiogenesis therapy. Methods We conducted a retrospective analysis of NSCLC patients who underwent next-generation sequencing test (either 295-gene panel NGS or 1021-gene panel NGS) from September 2017 to November 2020. The relationship between TMB and smoking status was investigated. Kaplan–Meier survival analysis was used to compare progression-free survival (PFS) of the NSCLC patients who received combination immunotherapy grouped by TMB value and smoking status. Results We enrolled 323 cases and 388 cases of NSCLC patients in the 295-gene panel cohort and 1021-gene panel cohort, respectively. Positive correlation between TMB and smoking status was found in lung adenocarcinoma, but not in lung squamous cell carcinoma. Participants with both high TMB and smoking status who received immune checkpoint therapy combined with chemotherapy or anti-angiogenesis therapy had longer PFS than other participants (p < 0.05). Conclusions The combination of TMB with smoking status might be a potential predictor for the efficacy of combination immunotherapy in advanced NSCLC.

Introduction: There is still lack of specific biomarkers in predicting the radiosensitivity of non-small cell lung cancer (NSCLC) patients in clinic. Previous studies have shown that the EGFR gene status may correlate with radiosensitivity of NSCLC. However, the underlying mechanisms remain unknown. The aim of this study was to further investigate the correlation between EGFR mutation status and the NSCLC cell radiosensitivity and to explore the possible cellular mechanism. Methods: Eight NSCLC cell lines with different EGFR gene status were irradiated by linear accelerator, and the radiosensitivity between the cell lines was compared by cell colony formation assay and cell proliferation assay. Cell cycle and apoptosis were analysed by flow cytometry. Radiosensitivity-related protein expression was detected by Western blotting. Results: In the present study, we found that NSCLC cell lines with the epidermal growth factor receptor (EGFR) gene mutations were more sensitive to X-ray irradiation than those with wild-type EGFR (P<0.05). No difference in radiosensitivity was observed between NSCLC cells with EGFR exon19 deletion (Del 19) mutation and exon 21 point mutation at position 858 (L858R) with or without T790M mutation (P<0.05), as well as between NSCLC cells with EGFR mutation and those with acquired EGFR-tyrosine kinase inhibitors (TKIs) resistance. Mechanistically, EGFR mutations promoted NSCLC cell apoptosis in response to X-ray irradiation through the upregulation of proapoptotic protein Bax and downregulation of anti-apoptotic proteins such as Bcl-2 and DNA-dependent protein kinase catalytic subunit. In addition, phosphorylated histone (γ-H2AX) foci assay showed that EGFR mutations sustained irradiation-induced DNA damage. Conclusion: Taken together, our study demonstrates that EGFR mutations are closely associated with the increased sensitivity of NSCLC cell lines to X-ray irradiation and that EGFR mutation status is a potentially useful indicator to evaluate the effectiveness of radiotherapy in the treatment of NSCLC.

Background: There is no satisfactory indicator for monitoring recurrence after resection of hepatocellular carcinoma (HCC). This retrospective study aimed to design and validate an HCC monitor recurrence (HMR) model for patients without metastasis after hepatectomy. Methods: A training cohort was recruited from 1179 patients with HCC without metastasis after hepatectomy between February 2012 and December 2015. An HMR model was developed using an AdaBoost classifier algorithm. The factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated based on the area under the receiver operating characteristic curves (AUCs). The model was validated using a cohort of 695 patients. Results: In preoperative patients with positive or negative AFP, the AUC of the validation cohort in the HMR model was .8877, which indicated better diagnostic efficacy than that of serum AFP (AUC, .7348). The HMR model predicted recurrence earlier than computed tomography/magnetic resonance imaging did by 191.58 ± 165 days. In addition, the HMR model can predict the prognosis of patients with HCC after resection. Conclusions: The HMR model established in this study is more accurate than serum AFP for monitoring recurrence after hepatectomy for HCC and can be used for real-time monitoring of the postoperative status in patients with HCC without metastasis.