The benefit of adjuvant chemotherapy (ACT) remains unknown for patients with stage I lung adenocarcinoma (ADC) with spread through air spaces (STAS). This study investigated the effect of adjuvant chemotherapy in stage I ADC/STAS-positive patients. A total of 3346 patients with stage I ADC from five institutions in China were identified from 2009 to 2013, of whom 1082 were diagnosed with STAS (32.3%). By using the Kaplan–Meier method and Cox proportional hazard regression model, we explored the impact of STAS on prognosis, and determined if the use of adjuvant chemotherapy was associated with improved outcomes in patients with stage I ADC/STAS-positive. A validation cohort was also included in this study. Patients with stage I ADC/STAS-positive in the primary cohort had unfavorable overall survival (OS) and disease-free survival (DFS). A multivariate Cox regression model confirmed the survival disadvantages of STAS in patients with stage I ADC [OS: hazards ratio (HR) = 1.877, 95% confidence interval (CI): 1.579–2.231; p < 0.001; DFS: HR = 1.895, 95% CI: 1.614–2.225; p < 0.001]. Lobectomy was associated with better OS and DFS than sublobar resection (SR) in both stage IA and IB ADC/STAS-positive. Similar results were observed in the validation cohort. For patients with stage IB ADC/STAS-positive, ACT was revealed as an independent factor for favorable survival (OS: HR = 0.604, 95% CI: 0.397–0.919; p = 0.018; DFS: HR = 0.565, 95% CI: 0.372–0.858; p = 0.007). However, among patients with stage IA ADC/STAS-positive, ACT was associated with improved outcomes only for those undergoing SR (OS: HR = 0.787, 95% CI: 0.359–0.949; p = 0.034; DFS: HR = 0.703, 95% CI: 0.330–0.904; p = 0.029). The presence of STAS was correlated with poor prognosis in patients with stage I ADC. Our study suggested that ACT might be considered for patients with stage IB ADC/STAS-positive and those with stage IA ADC/STAS-positive who underwent SR.

There is increasing evidence that inflammation-based biomarkers are associated with tumor microenvironment which plays important roles in cancer progression. A high lymphocyte-to-monocyte ratio (LMR), has been suggested to indicate favorable prognoses in various epithelial cancers. We performed a meta-analysis to quantify the prognostic value of LMR in advanced-stage epithelial cancers undergoing various treatment. We searched PubMed, EMBASE, Web of science and Cochrane Library up to July 2018 for relevant studies. We included studies assessing the prognostic impact of pretreatment LMR on clinical outcomes in patients with advanced-stage epithelial cancers. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. A total of 8984 patients from 35 studies were included. A high pretreatment LMR was associated with favorable OS (HR = 0.578, 95% CI 0.522–0.641, P < 0.001) and PFS (HR = 0.598, 95% CI 0.465–0.768, P < 0.001). The effect of LMR on OS was observed among various tumor types. A higher pretreatment LMR was associated with improved OS in chemotherapy (n = 10, HR = 0.592, 95% CI 0.518–0.676, P < 0.001), surgery (n = 10, HR = 0.683, 95% CI 0.579–0.807, P < 0.001) and combined therapy (n = 11, HR = 0.507, 95% CI 0.442–0.582, P < 0.001) in the subgroup analysis by different therapeutic strategies. The cut-off value for LMR was 3.0 (range = 2.35–5.46). Subgroup analysis according to the cut-off value showed a significant prognostic value of LMR on OS and PFS in both subgroups. A high pretreatment LMR is associated with favorable clinical outcomes in advanced-stage epithelial cancers undergoing different therapeutic strategies. LMR could be used to improve clinical decision-making regarding treatment in advanced epithelial cancers.

Background and Objective: Increasing evidence has elucidated the clinicopathological significance of individual TME component in predicting outcomes and immunotherapeutic efficacy in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate whether comprehensive TME-based signatures could predict patient survival and therapeutic responses in LUAD, and to assess the associations among TME signatures, single nucleotide variations and clinicopathological characteristics.Methods: In this study, we comprehensively estimated the TME infiltration patterns of 493 LUAD patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathological features of LUADs using two proposed computational algorithms. A TMEscore was then developed based on the TME signature genes, and its prognostic value was validated in different datasets. Bioinformatics analysis was used to evaluate the efficacy of the TMEscore in predicting responses to immunotherapy and chemotherapy.Results: Three TME subtypes were identified with no prognostic significance exhibited. Among them, naïve B cells accounted for the majority in TMEcluster1, while M2 TAMs and M0 TAMs took the largest proportion in TMEcluster2 and TMEcluster3, respectively. A total of 3395 DEGs among the three TME clusters were determined, among which 217 TME signature genes were identified. Interestingly, these signature genes were mainly involved in T cell activation, lymphocyte proliferation and mononuclear cell proliferation. With somatic variations and tumor mutation burden (TMB) of the LUAD samples characterized, a genomic landscape of the LUADs was thereby established to visualize the relationships among the TMEscore, mutation spectra and clinicopathological profiles. In addition, the TMEscore was identified as not only a prognosticator for long-term survival in different datasets, but also a predictive biomarker for the responses to immune checkpoint blockade (ICB) and chemotherapeutic agents. Furthermore, the TMEscore exhibited greater accuracy than other conventional biomarkers including TMB and microsatellite instability in predicting immunotherapeutic response (p < 0.001).Conclusion: In conclusion, our present study depicted a comprehensive landscape of the TME signatures in LUADs. Meanwhile, the TMEscore was proved to be a promising predictor of patient survival and therapeutic responses in LUADs, which might be helpful to the future administration of personalized adjuvant therapy.

Background: Adjuvant chemotherapy (ACT) is routinely the recommended treatment for patients with advanced non-small cell lung cancer (NSCLC) but remains a controversial option in stage IB patients. We therefore pooled the current evidence to determine the prognostic impact of ACT in stage IB NSCLC patients in the context of the eighth tumor, node, metastasis (TNM) staging system. Methods: Five electronic databases were searched for eligible studies up to December 2020 without language restrictions. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS). Search results were filtered by a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The risk of bias was assessed independently using a modified set. Stata 16.0 was used for general data analysis and meta-analysis, and subgroup analyses were performed to investigate the source of interstudy heterogeneity. Results: In all, 12 eligible studies were identified and 15,678 patients included. Our results demonstrated that ACT was associated with improved OS [n=11; hazard ratio (HR) =0.65; 95% confidence interval (CI): 0.60–0.70; P<0.001; I²=33.4%, P=0.131] and DFS (n=9; HR =0.73; 95% CI: 0.63–0.83; P<0.001; I²=66.7%, P=0.002) in stage IB NSCLC patients. Subgroup analysis by histology indicated that administration of ACT conferred more favorable survival to both stage IB squamous cell carcinoma (n=1; HR =0.56; 95% CI: 0.28–0.84; P<0.001) and adenocarcinoma (n=6; HR =0.59; 95% CI: 0.47–0.71; P<0.001; I²=31.0%, P=0.203). Meanwhile, both platinum-based ACT (n=7; HR =0.62; 95% CI: 0.51–0.74; P<0.001; I²=44.8%, P=0.093) and other regimens (n=2; HR =0.66; 95% CI: 0.61–0.72; P<0.001; I²=0.7%, P=0.316) could benefit patients with stage IB disease. Discussion: ACT might provide survival benefits to patients with stage IB NSCLC irrespective of histology or regimens. Patient selection and time trend biases were inevitable due to the limitation of retrospective studies. More prospective studies should be initiated to investigate the optimal ACT regimens in different histologic types in stage IB NSCLC patients.

This review explores the intricate roles of metal ions—iron, copper, zinc, and selenium—in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.