Background Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism. Methods Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS). This meta-analysis was registered with PROSPERO (CRD42022298439). Results Sixteen RCTs, involving 10,155 patients with advanced NSCLC, was collected in this meta-analysis. The pooled HR comparing immunotherapy vs non-immunotherapy were 0.76 (95%CI 0.71–0.81) for males and 0.74 (95%CI 0.63–0.87) for females. The pooled HRs comparing immune-checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy were 0.79 (95%CI 0.70–0.89) for males and 0.63 (95%CI 0.42–0.92) for females. The pooled HRs comparing ICIs versus chemotherapy were 0.74 (95%CI 0.67–0.81) for males and 0.83 (95%CI 0.73–0.95) for females. In squamous NSCLC, the pooled HRs comparing immunotherapy vs non-immunotherapy were 0.73 (95%CI 0.58–0.91) for males and 0.74 (95%CI 0.37–1.48) for females. In non-squamous NSCLC, the pooled HRs comparing immunotherapy versus non-immunotherapy were 0.62 (95%CI 0.71–0.94) for males and 0.59 (95%CI 0.39–0.89) for females. Conclusion Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy. KEY MESSAGE Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC.

Background With the use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination vs chemotherapy in patients with advanced or metastatic NSCLC. Methods This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). This meta-analysis’s Prospero registration number is CRD42022323570. Results The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both OS [HR = .75, 95% CI (.70-.80), P < .001] and PFS [HR = .83, 95% CI (.73-.95), P < .001]. Besides, ICIs were associated with fewer AEs compared to chemotherapy. Conclusion PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in advanced or metastatic NSCLC.

Background: Lung adenocarcinoma (LUAD) is a sex-biased and easily metastatic malignant disease. A signature based on 5 long non-coding RNAs (lncRNAs) has been established to promote the overall survival (OS) prediction effect on LUAD.Methods: The RNA expression profiles of LUAD patients were obtained from The Cancer Genome Atlas. OS-associated lncRNAs were identified based on the differential expression analysis between LUAD and normal samples followed by survival analysis, univariate and multivariate Cox proportional hazards regression analyses. OS-associated lncRNA with sex dimorphism was determined based on the analysis of expression between males and females. Functional enrichment analysis of the Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to explore the possible mechanisms of 5-lncRNA signatures.Results: A 5-lncRNA signature (composed of AC068228.1, SATB2-AS1, LINC01843, AC026355.1, and AL606489.1) was found to be effective in predicting high-risk LUAD patients as well as applicable to female and male subgroups and &lt;65-year and ≥65-year age subgroups. The forecasted effect of the 5-lncRNA signature was more efficient and stable than the TNM stage and other clinical risk factors (such as sex and age). Functional enrichment analysis revealed that the mRNA co-expressed with these five OS-related lncRNAs was associated with RNA regulation within the nucleus. AL606489.1 demonstrated a sexual dimorphism that may be associated with microtubule activity.Conclusion: Our 5-lncRNA signature could efficaciously predict the OS of LUAD patients. AL606489.1 demonstrated gender dimorphism, which provides a new direction for mechanistic studies on sexual dimorphism.

Background Lung adenocarcinoma (LUAD) is a sex-biased and easily metastatic malignant disease. A signature based on 5 long non-coding RNAs (lncRNAs) has been established to promote the overall survival (OS) prediction effect on LUAD. Methods The RNA expression profiles of LUAD patients were obtained from The Cancer Genome Atlas. OS-associated lncRNAs were identified based on the differential expression analysis between LUAD and normal samples followed by survival analysis, univariate and multivariate Cox proportional hazards regression analyses. Prognostic lncRNA with sex dimorphism was determined based on the analysis of expression between men and women. Functional enrichment analysis of the Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to explore the possible mechanisms of 5-lncRNA signatures. Results A 5-lncRNA signature (composed of AC068228.1, SATB2-AS1, LINC01843, AC026355.1, and AL606489.1) was found to be effective in predicting high-risk LUAD patients as well as applicable to female and male subgroups and < 65-year and ≥ 65-year age subgroups. The forecasted effect of the 5-lncRNA signature was more efficient and stable than the TNM stage and other clinical risk factors (such as sex and age). Functional enrichment analysis revealed that the mRNA co-expressed with these five OS-related lncRNAs was associated with RNA regulation within the nucleus. AL606489.1 demonstrated a sexual dimorphism that may be associated with microtubule activity. Conclusion Our 5-lncRNA signature could efficaciously predict the OS of LUAD patients. AL606489.1 demonstrated gender dimorphism, which provides a new direction for mechanistic studies on sexual dimorphism.