Objective: This study aimed to comprehensively investigate the regulatory mechanism and clinical value of secreted phosphoprotein 1 (SPP1) in the three-stage progression of "smoking-chronic obstructive pulmonary disease (COPD)-carcinogenesis" in lung squamous cell carcinoma (LUSC) through integrated bioinformatics analysis and machine learning. Methods: The datasets for the three stages of LUSC were downloaded from the Gene Expression Omnibus (GEO) database, including GSE18385 (containing lung tissue samples from 31 healthy smokers and 21 healthy non-smokers), GSE38974 (containing lung tissue samples from 23 smoking COPD patients and 9 healthy smokers), and GSE12472 (containing lung tissue samples from 18 LUSC patients with COPD and 17 smoking COPD patients). The Cancer Genome Atlas (TCGA)-LUSC dataset (comprising 504 samples, including lung tissue samples from LUSC patients and their matched normal lung tissue samples) was downloaded from TCGA database for further analysis. Samples and follow-up information from 208 non-small cell lung cancer patients who underwent radical resection and mediastinal lymph node dissection at Zhongshan Hospital, Fudan University in 2005 were selected for prognostic analysis and validation. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to screen stage-specific module genes. Differentially expressed genes (DEGs) were identified through differential expression analysis. The CIBERSORT algorithm and Gene Set Enrichment Analysis (GSEA) were used to characterize the immune microenvironment. Eight machine learning algorithms and protein-protein interaction (PPI) network analysis were combined to screen for core regulatory targets. Results: Results from WGCNA and differential analysis of the GEO datasets indicated that SPP1 is consistently highly expressed across the three stages of LUSC. Analysis of the TCGA-LUSC dataset further verified that the relative expression level of SPP1 in lung tissues of LUSC patients was significantly higher than in normal lung tissues (9.13±2.01 vs 4.68±1.64, P<0.001). Furthermore, SPP1 expression was significantly higher in patients with TNM stage Ⅲ than in those with stage Ⅱ (9.59±2.09 vs 8.80±2.15, P=0.045). Male LUSC patients with high smoking exposure exhibited higher SPP1 expression levels than those with low smoking exposure (9.56±2.23 vs 8.60±2.04, P=0.032). Survival prognosis analysis revealed that among male patients, the difference in median overall survival (OS) between the high SPP1 expression group and the low expression group was statistically significant [2.90 (95%CI: 2.11-4.64) years vs 4.69 (95%CI: 2.95-7.34) years, P=0.032). Data validation from Zhongshan Hospital, Fudan University, also showed that the 5-year survival rate of lung cancer patients with high SPP1 expression was lower than that of patients with low SPP1 expression (49.3% vs 62.6%, P=0.042). Results from the CIBERSORT algorithm indicated that high SPP1 expression drives increased infiltration of M2 macrophages (P<0.001). Machine learning combined with PPI network analysis identified NTN1 and CX3CL1 as key regulatory targets of SPP1, which may be associated with the occurrence and development of lung cancer. Conclusion: SPP1 may promote LUSC progression by mediating M2 macrophage polarization through suppressing NTN1 or activating CX3CL1, suggesting its potential as a prognostic biomarker and therapeutic target for high-risk male smokers.

Objective: To analyze the mutational landscape of primary and acquired mesenchymal to epithelial transition factor (MET) mutations in non-small cell lung cancer (NSCLC) and investigate the impact of co-mutations on the therapeutic efficacy. Methods: A total of 316 pathologically confirmed NSCLC patients with MET gene mutations treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Shanghai Chest Hospital, Shanghai Jiao Tong University, between January 2012 and May 2023 were retrospectively enrolled. Demographics, clinicopathological characteristics, and treatment outcomes were collected. Patients were classified into primary MET mutation and acquired MET mutation groups according to the timing of mutation occurrence, and intergroup differences were compared. Treatment responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. Follow-up data on efficacy and progression-free survival (PFS) were collected through telephone calls and medical record review. The follow-up continued until January 2024. Kaplan-Meier survival curves were generated, and log-rank tests were used to compare PFS between patients with different co-mutations receiving tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) therapy. Results: Compared to the acquired mutation group, patients with primary MET mutations were significantly older[median (Q1, Q3) age: 65 (58, 71) vs 59 (51, 64) years; P<0.001], had a higher proportion of males [62.4% (141/226) vs 48.9% (44/90), P=0.028] and a higher proportion of never-smokers [48.7% (110/226) vs 30% (27/90), P=0.002]. In the primary mutation group, TP53 was the most common co-mutation gene (43%, 51/118), followed by EGFR (32%, 38/118) and KRAS (9%, 11/118). In the acquired mutation group, 89% (69/73) of patients retained the EGFR mutation. Aside from EGFR, the most common co-mutation genes were TP53 (63%, 46/73) and CDK4 (12%, 9/73). Among the 62 patients treated with MET-TKI, those with concurrent EGFR-sensitive mutations had a median PFS of 3.1 (95%CI: 2.4-7.2) months, significantly shorter than that of EGFR wild-type patients [18.2 (95%CI: 9.2-22.1) months, P<0.001]. Patients with TP53 co-mutations had a median PFS of 7.5 (95%CI: 6.4-not reached) months, which was significantly longer than TP53 wild-type patients [3.4 (95%CI: 1.8-4.3) months, P=0.035]. Among the 57 patients treated with ICI, those with EGFR-sensitive mutations had a median PFS of 5.3 (95%CI: 2.0-8.2) months, which was significantly shorter than EGFR wild-type patients [10.4 (95%CI: 5.2-not reached) months, P=0.027]. Patients with TP53 co-mutations had a median PFS of 5.9 (95%CI: 3.8-20.4) months, which was longer than TP53 wild-type patients [3.0 (95%CI: 2.0-4.5) months], although the difference was not statistically significant (P=0.344). Conclusions: Primary and acquired MET mutations in NSCLC exhibit distinct genomic characteristics. Patients harboring concurrent EGFR mutations in NSCLC may derive less benefit from MET-TKI and ICI, whereas those harboring TP53 co-mutations tend to experience more favorable outcomes compared with TP53 wild-type NSCLC patients when treated with MET-TKI.

To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT).

To investigate the oncogenic role of circular RNA circ_EPHB4 in glioma and its molecular mechanism.

Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer morbidity and mortality worldwide, and its initiation and progression are closely associated with the tumor immune microenvironment. Increasing evidence suggests that environmental exposure is a critical factor influencing lung cancer development. Among these factors, fine particulate matter (PM2.5), a major component of air pollution, has been strongly linked to elevated lung cancer risk and unfavorable prognosis. However, the underlying immunoregulatory mechanisms by which PM2.5 drives LUAD progression remain poorly understood. Tumor-associated macrophages (TAMs), especially those polarized toward the M2 phenotype, are key components of the tumor microenvironment and play crucial roles in tumor growth, angiogenesis, and immune evasion. This study aims to investigate the effects of PM2.5 exposure on TAMs and to identify the key pro-tumorigenic factors mediating this process.

Lung cancer currently ranks first globally in both incidence and mortality. Pemetrexed (PMX) serves as a first-line treatment for lung adenocarcinoma (LUAD), but the patients often develop drug resistance during therapy. Milk exosome (mEXO) have the advantages of low immunogenicity, high tissue affinity, and low cost, and mEXO itself has anti-tumor effects. Hyaluronan (HA) naturally bind to CD44, a receptor which is highly expressed in LUAD tissues. This study aims to construct hyaluronan-modified milk exosome (HA-mEXO) and preliminarily investigate their molecular mechanisms for reversing PMX resistance through cellular experiments.

Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.

KRAS mutations are major oncogenic drivers in colorectal cancer (CRC), occurring in 35%-49% of cases; of which 3%-4% involve the KRAS G12C subtypes, characterized by a glycine-to-cysteine substitution at codon 12. This variant is associated with poor treatment response and reduced overall survival. Recent phase I/II trials of KRAS G12C inhibitors have shown promising results, and the phase III CodeBreaK 300 study confirmed that sotorasib combined with panitumumab significantly improved efficacy compared with standard treatment, establishing a new therapeutic option for KRAS G12C-mutant metastatic CRC. However, drug resistance inevitably develops, driven by mechanisms such as feedback activation of signaling pathways, secondary mutations, and epithelial-mesenchymal transition. Strategies under investigation include targeting alternative signaling pathways, developing next-generation inhibitors and specific degraders, and exploring multi-mechanism or multi-target combination strategies. This review systematically outlines the development of KRAS G12C inhibitors in mCRC, summarizes resistance mechanisms, and discusses emerging combination regimens, aiming to provide a theoretical basis and future directions for treatment optimization.

To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.

Objective: To explore the association of 21-gene recurrence score (RS) and clinicopathologic characteristics of hormone receptor (HR) positive T1-3N1M0 breast cancer and its value in prognosis evaluation. Methods: The clinicopathological data of 287 patients with T1-3N1M0 breast cancer were collected, the 21-gene assay was completed, and follow-up was conducted. According to the 21-gene RS, the patients were divided into the RS<26 and RS≥26 groups. The relationship between the 21-gene RS and clinicopathological characteristics, treatment, recurrence, and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for disease free survival (DFS). Results: The median RS of the 287 patients was 16. There were 240 cases with RS <26 and 47 cases with RS≥26. Tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 index were significantly different between the two cohorts (P<0.05 for all). After a median follow-up of 74 months, the recurrence rate in the RS<26 group (8.3%) was significantly lower than that in the RS≥26 group (23.4%), the locoregional recurrence (LRR) rates in the RS<26 and RS≥26 groups were 2.1% and 0%,and the distant metastasis (DM) rates were 6.3% and 23.4%, respectively. The 5-year relapse free survival (RFS) rates of patients with RS<26 and RS≥26 were 93.8% (95% CI: 90.7%-96.9%) and 87.2% (95% CI: 78.2%-97.3%), and the 5-year DFS rates were 92.1% (95% CI: 88.7%-95.6%) and 85.1% (95% CI: 75.5%-95.9%), respectively, with significant differences between the two cohorts (P=0.007 and P=0.006, respectively). Univariate analysis showed age, tumor size, grade, PR status, Ki-67 index and RS were prognostic factors for DFS (P<0.05 for all). Multivariate analysis showed that age and tumor size were independent significant predictors for DFS (P<0.05). Conclusions: The 21-gene RS of T1-3N1M0 breast cancer is related to tumor size, grade, ER, PR, and Ki-67 index. RS is an important factor affecting DM and DFS.

Fusion genes represent a core molecular mechanism in the pathogenesis of acute promyelocytic leukemia (APL). In recent years, a novel type of tripartite retinoic acid receptor (RAR) fusion genes has been identified in atypical APL (aAPL), exhibiting distinct structural characteristics and pathogenic mechanisms compared to the classical bipartite fusion. This article systematically introduces relevant content in this field: it begins by outlining the long-standing scientific puzzle of inconsistent clinical resistance versus in vitro sensitivity in aAPL patients; subsequently, it describes the discovery process and structural features of tripartite fusion genes in all RARG and specific RARA-related cases, and elucidates the key molecular mechanism by which tripartite fusion leads to all-trans retinoic acid (ATRA) resistance at the protein conformational level; finally, the discovery of transposon involvement in the formation of tripartite fusions and its implications for the mechanism of fusion gene are discussed.

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylic acid cycle and one of the common mutated genes in AML. Although the 2022 version of the ELN guidelines suggests that IDH mutations cannot be used as a separate prognostic stratification indicator, multiple studies have indicated that IDH mutations have prognostic significance for AML. Early identification of IDH mutations and selection of appropriate treatment options are crucial. This review summarizes the research progress on the characteristics, carcinogenic mechanisms, prognosis of IDH mutations in AML patients, and treatment options, in order to provide reference for further improving the prognosis of IDH -mutated AML patients.

To analyze the clinical features of acute myeloid leukemia patients with DEK-NUP214 fusion gene positive.

To explore the correlation between single nucleotide polymorphisms (SNPs) of ARID5B gene and the risk of acute lymphoblastic leukemia (ALL) and minimal residual disease (MRD) in children of Hui and Han nationality in Ningxia.

To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene.

Objective: To investigate the clinical significance of monitoring SIL::TAL1 fusion transcripts in the evaluation of treatment response and prognosis of children with T-acute lymphoblastic leukemia (T-ALL). Methods: A retrospective cohort study was conducted to analyze the clinical data of 46 newly diagnosed pediatric T-ALL with SIL::TAL1 fusion transcripts treated at Beijing Children's Hospital Capital Medical University from November 2004 to December 2022. The SIL::TAL1 fusion transcripts were quantitatively detected at the initial diagnosis (TP0) and early stage of induction therapy (TP1), at the end of induction remission therapy (TP2), before consolidation therapy (TP3) and subsequent treatment. Patients were divided into negative and positive groups on SIL::TAL1 fusion transcripts level, differences of clinical features and survival among groups at TP0 to TP3 were analyzed. The χ2 test or Fisher exact test or Mann-Whitney U test was used to compare the clinical difference. Survival analysis was estimated by Kaplan-Meier method with Log-Rank testing. Multivariate analysis was conducted by Cox proportional hazards models. Results: Among the 46 children with SIL::TAL1 fusion transcripts, 36 were males and 10 were females, with the onset age of 6.8 (3.4, 9.5) years. The negative rates of SIL::TAL1 fusion transcripts for TP1,TP2, TP3, before delayed intensification Ⅰ treatment (TP4), before maintenance therapy (TP5) were 36% (13/36), 78% (32/41), 76% (32/42), 15/16, and 12/12, respectively. No significant difference was found on clinical features and prednisone response between groups at TP0-TP3 (all P>0.05). The 5-year events free survival (EFS) rate of patients classified as negative (32 cases) and positive (9 cases) groups at TP2 was (78±8)% and (33±16)%, respectively (χ2=9.86, P=0.002), the 5-year overall survival (OS) rate was (81±7)% and (44±17)%, respectively (χ2=6.40, P=0.011). The 5-year EFS rate of patients classified as negative (32 cases) and positive (10 cases) groups at TP3 was (78±8)% and (30±15)%, respectively (χ2=13.04, P<0.001) and the 5-year OS rate was (84±6)% and (30±15)%, respectively (χ2=15.95, P<0.001). Cox multivariate regression showed that positive of SIL::TAL1 transcript at TP3 was adverse independent prognostic factors for EFS and OS (EFS: HR=6.70, 95%CI 2.01-22.35, P=0.002; OS: HR=10.73, 95%CI 2.50-46.09, P=0.001). Conclusions: Monitoring SIL::TAL1 fusion transcripts can reflect the clinical treatment response. The level of SIL::TAL1 fusion transcripts at early period can predict long-term outcomes of these patients.

To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).

The clinical data of patients with acute myeloid leukemia (AML) treated at Hebei Yanda Lu Daopei Hospital between August 1, 2024, and March 1, 2025 were retrospectively included, to differentiate AML with the same recurrent t(11;12)(p15;q13) karyotype but harboring distinct rare fusion genes, namely NUP98::RARG::LINE-L2a and NUP98::HOXC13. Two patients were included: Patient 1, a 12-year-old male, visited Hebei Yanda Lu Daopei Hospital on August 8, 2024, due to "fever for 4 days accompanied by sore throat"; Patient 2, a 33-year-old female, visited the hospital on September 22, 2024, due to "recurrent fatigue and cough for over one month". Case 1 and Case 2 carried the NUP98::RARG::LINE-L2a and NUP98::HOXC13 fusion genes, respectively. The patient with NUP98::RARG::LINE-L2a fusion genes exhibited bone marrow morphology and immunophenotypic features resembling acute promyelocytic leukemia (APL) but was resistant to all-trans retinoic acid. Although initial treatment achieved remission, early relapse occurred. The patient with NUP98::HOXC13 fusion genes showed increased myeloblasts, the presence of Auer rods, and an elevated proportion of promyelocytes, along with mutations in FLT3-TKD gene, RUNX1 gene and, WT1 gene, demonstrating resistance to multiple chemotherapy regimens. Both patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) without achieving complete remission. After transplantation, they were followed for 8 and 9 months, respectively, with quantitative monitoring of fusion genes showing negative results. Although the patients with NUP98::RARG::LINE-L2a and NUP98::HOXC13 fusion genes have completely identical chromosomal abnormalities, but they are different rare molecular subtypes. Both involve the NUP98 gene. The former partner gene is RARG, with clinical manifestations, bone marrow morphology, and immunophenotype similar to APL. The latter partner gene is HOXC13, with the characteristics of NUP98-AML patients.