Exploring the Common Genetic Underpinnings of Chronic Pulmonary Disease and Esophageal Carcinoma Susceptibility.

Background: Pulmonary diseases and esophageal cancer are highly prevalent conditions with rising incidence worldwide. Prior evidence supports shared environmental and behavioral factors, but less is known regarding potential genetic links underlying this comorbidity. This study aimed to elucidate the complex genetic relationship between chronic lung diseases and esophageal cancer risk. Methods: Linkage disequilibrium score regression assessed the genetic correlation between esophageal cancer and asthma, COPD, and idiopathic pulmonary fibrosis leveraging extensive GWAS datasets. Pleiotropic analysis, gene-set enrichment, eQTL mapping, and mendelian randomization causality analyses were then conducted to identify specific shared genetic variants, enriched pathways, causal relationships and gene regulatory mechanisms connecting lung disease and cancer susceptibility. Results: Significant genetic correlations were observed between esophageal cancer and both COPD and asthma, but not idiopathic pulmonary fibrosis. Further analyses identified 13 pleiotropic loci and 6 shared genes including CHRNA4, ERBB3, and SMAD3, as well as pathways related to immune function. eQTL integration highlighted 53 genes like SOCS1, FGF2, and CHRNA5 with tissue-specific regulatory effects on disease risk. Bidirectional relationships were noted, whereby genetic predisposition to asthma and COPD increased esophageal cancer risk, while cancer liability reciprocally raised pulmonary fibrosis risk. Conclusions: These genomic analyses provide initial evidence that shared genetic factors may underpin the comorbidity between lung conditions and esophageal malignancy. The genes and pathways identified offer insights into biological mechanisms linking both diseases, aiding future screening, prevention and therapeutic efforts to mitigate this growing comorbidity burden.

Comparison of supraclavicular surgery plus radiotherapy versus radiotherapy alone in breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastasis: A multicenter retrospective study.

PURPOSE: To evaluate and compare the outcomes of supraclavicular lymph node dissection plus radiotherapy (RT) and RT alone for patients with synchronous ipsilateral supraclavicular lymph node metastasis. METHODS: In all, 293 patients with synchronous ipsilateral supraclavicular lymph node metastasis across three centers were included. Of these, 85 (29.0%) received supraclavicular lymph node dissection plus RT (Surgery + RT) and 208 (71.0%) received RT alone. All patients received preoperative systemic therapy followed by mastectomy or lumpectomy and axillary dissection. Supraclavicular recurrence-free survival (SCRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated by using the Kaplan-Meier method and multivariate Cox models. Multiple imputation was used for missing data. RESULTS: The median follow-up duration of the RT and Surgery + RT groups were 53.7 and 63.5 months, respectively. For the RT and Surgery + RT groups, the 5-year SCRFS rates were 91.7% vs. 85.5% (P = 0.522), LRRFS rates were 79.1% vs. 73.1% (P = 0.412), DMFS rates were 60.4 vs. 58.8% (P = 0.708), DFS rates were 57.6% vs. 49.7% (P = 0.291), and OS rates were 71.9% vs. 62.2% (P = 0.272), respectively. There was no significant effect on any outcome when comparing Surgery + RT versus RT alone in the multivariate analysis. Based on four risk factors of DFS, patients were classified into three risk groups: the intermediate- and high-risk groups had significantly lower survival outcomes than the low-risk group. Surgery + RT did not improve outcomes of any risk group compared with RT alone. CONCLUSIONS: Patients with synchronous ipsilateral supraclavicular lymph node metastasis may not benefit from supraclavicular lymph node dissection. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups.

Systematic expression analysis of the CELSR family reveals the importance of CELSR3 in human lung adenocarcinoma.

Cadherin EGF LAG seven-pass G-type receptors (CELSRs) are involved in the progression of various types of cancer. CELSR3, a crucial signalling molecule in the WNT/PCP pathway, is believed to be associated with tumorigenesis and metastasis. However, its role in lung adenocarcinoma (LUAD) remains unclear. In this paper, we analysed the expression of CELSR family members using the Oncomine, GEPIA and UALCAN databases. We used a Kaplan-Meier plotter to assess the effect of CELSRs on tumour prognosis. Next, gene ontology (GO), KEGG pathway, miRNA target, kinase target and transcription factor-target enrichment were analysed by GSEA. Simultaneously, we conducted functional assays including cell viability, colony formation and transwell assays, to determine the oncogenic role of CELSR3 in LUAD. Finally, we used the TIMER and TISIDB databases to analyse the correlation between CELSR3 and immune infiltration and the potential chemokine receptor axis causing immune cell expression. High expression of CELSR3 is in LUAD predicts poor prognosis and early progression of the tumour. KEGG and GO enrichment analysis revealed the functional relationship between CELSR3 and cell adhesion, the cell cycle, and DNA replication. Down-regulation of CELSR3 suppressed cell proliferation to a significant extent, in addition to inhibiting invasion and migration in LUAD cells. Finally, CELSR3 expression was significantly correlated with the infiltration level of CD8+T cells through the CCL17/CCR4 axis in LUAD. These results indicate that CELSR3 can serve as a prognostic biomarker for determining prognosis and immune infiltration in LUAD.

Can internal mammary lymph nodes irradiation bring survival benefits for breast cancer patients? A systematic review and meta-analysis of 12,705 patients in 12 studies.

OBJECTIVE: To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in breast cancer patients. METHODS: The computer searched PubMed, EMBASE, Web of science, CNKI, Wanfang Medical Network, the Chinese Biomedical Literature Database to find clinical studies on internal mammary lymph node irradiation (IMNI) in breast cancer. The quality of the included literature was evaluated according to the Newcastle-Ottawa scale. Stata14 software was used for meta-analysis. RESULTS: A total of 12,705 patients in 12 articles were included for meta-analyzed. Compared with patients who unirradiated internal mammary lymph nodes (non-IMNI), the risk of death for patients after IMNI was reduced by 11% (HR 0.89, 95% CI 0.79-1.00, P = 0.0470); DFS of group mixed N+ patients (high risk group) was significantly improved after IMNI (HR 0.58, 95% CI 0.49-0.69, P < 0.001). Further subgroup analysis shows that compared with non-IMNI, DFS was significantly increased in N1or ypN1 subgroup (HR 0.65, 95% CI 0.49-0.87, P = 0.003) and N2or ypN2 subgroup (HR 0.51, 95% CI 0.37-0.70, P < 0.001) after IMNI, but there was no statistical difference in DFS between the IMNI and non-IMNI groups in N0 subgroup (HR 1.02 95% CI 0.87-1.20, P = 0.794) and N3 or ypN3 subgroup (HR 0.85, 95% CI 0.49-1.45, P = 0.547). No serious incidents were reported in all the included studies, and most of the acute and late side effects were mild and tolerable. CONCLUSION: Under modern radiotherapy techniques, IMNI can safely and effectively bring clinical benefits to N1-2 breast cancer patients, but its role in N0, N3 breast cancer patients remains to be further studied.

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer.

Cervical cancer (CC) is one of the most prevalent types of cancer affecting females worldwide. However, the molecular mechanisms underlying the development and progression of CC remains to be elucidated. Taking the high incidence and mortality rates amongst women into consideration, the identification of novel biomarkers to prevent CC is of great significance and required to improve diagnosis. Using three raw microarray datasets from the Gene Expression Omnibus database, 188 differentially expressed genes (DEGs) were identified. Gene Ontology and pathway analyses were performed on the DEGs. Through protein-protein interaction network construction and module analysis, eight hub genes [cell division cycle 6, cyclin-dependent kinase 1 (CDK1), cell division control protein 45, budding uninhibited by benzimidazoles 1 (BUB1), DNA topoisomerase II α (TOP2A) and minichromosome maintenance complex component 4, CCNB2 and CCNB1] were identified, but only TOP2A was considered a prognostic factor in survival analysis. There were strong positive correlations between TOP2A and BUB1 (P<0.0001, rs=0.635), CDK1 (P<0.0001, rs=0.511), centromere protein F (CENPF) (P<0.0001, rs=0.677), Rac GTPase activating protein 1 (RACGAP1) (P<0.0001, rs=0.612), F-box protein 5 (FBXO5) (P<0.0001, rs=0.585) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) (P<0.0001, rs=0.584). Additionally, BUB1, CDK1, CENPF, RACGAP1, FBXO5 and BUB1B are all potentially suitable candidate targets for the diagnosis and treatment of CC. In conclusion, the present study identified TOP2A as a potential tumor oncogene and a biomarker for the prognosis of CC.