bims-meluca 2021-12-12 papers

JTO Clin Res Rep. 2021 Dec;2(12): 100254

Obesity-Specific Association of Statin Use and Reduced Risk of Recurrence of Early Stage NSCLC.

Santosh K Patnaik, Cara Petrucci, Joseph Barbi, Robert J Seager, Sarabjot Pabla, Sai Yendamuri.

Introduction: Statins, used for their lipid-lowering activity, have anti-inflammatory and anticancer properties as well. We evaluated this potential benefit of statin use in patients with NSCLC.
Methods: All 613 patients with pathologic stage 1 or 2 NSCLC who had lobectomy without neoadjuvant therapy at our institution during 2008 to 2015 were included. Association between presurgery statin use and overall survival and recurrence-free survival (RFS) was analyzed using Cox proportional hazards regression. Association of statin use with tumor transcriptome was evaluated in another 350 lung cancer cases.
Results: Univariable analyses did not reveal a statistically significant association of statin use with either overall survival or RFS, with hazard ratio equals to 1.19 and 0.70 (Wald p = 0.28 and 0.09), respectively. In subgroup analyses, significantly improved RFS was found in statin users, but only in overweight/obese patients (body mass index [BMI] > 25; n = 422), with univariable and multivariable hazard ratio of 0.49 and 0.46 (p = 0.005 and 0.002), respectively, but not in patients with BMI less than or equal to 25 (n = 191; univariable p = 0.21). Transcriptomes of tumor statin users had high expression of tumoricidal genes such as granzyme A and interferon-γ compared with those of nonusers among high- but not low-BMI patients with lung cancer.
Conclusions: Our study suggests that statins may improve the outcome of early stage NSCLC but only in overweight or obese patients. This benefit may stem from a favorable reprogramming of the antitumor immune response that statins perpetrate specifically in the obese.

Keywords: Body mass index; Lung cancer; Obesity; Statin; Tumor immunity

DOI: https://doi.org/10.1016/j.jtocrr.2021.100254

Front Oncol. 2021 ;11 745150

The Survival Benefit for Optimal Glycemic Control in Advanced Non-Small Cell Lung Cancer Patients With Preexisting Diabetes Mellitus.

Jie Qian, Weimin Wang, Lin Wang, Jun Lu, Lele Zhang, Bo Zhang, Shuyuan Wang, Wei Nie, Yanwei Zhang, Yuqing Lou, Baohui Han.

Background: Diabetes mellitus (DM) is a frequent comorbidity in patients with cancer. This study aimed to evaluate the prognosis of advanced non-small cell lung cancer (NSCLC) patients with DM and to assess whether an optimal glycemic control improves overall survival (OS).
Methods: A total of 1279 advanced NSCLC patients including 300 (23.5%) with preexisting DM were retrospectively reviewed. The continuous relationship between glycated hemoglobin A1C (HbA1c) level and OS was analyzed by restricted cubic spline (RCS) function. Optimal HbA1c cut-off point was determined using X-tile analysis. Survival was analyzed with the Kaplan-Meier method and compared among groups stratified by diabetes status and HbA1c. Multivariable Cox proportional hazards regression analysis was employed to identify prognostic factors for OS after adjusting for baseline characteristics.
Results: DM and non-DM patients had similar OS (median (95% CI): 22.85 (20.05-26.73) vs. 22.22 (20.35-24.76) months, P=0.950). The multivariate Cox regression analyses showed that DM status was not a prognostic factor for OS (HR: 0.952, 95% CI: 0.808-1.122, P=0.559). However, there existed a non-linear but generally positive relationship between the elevated HbA1c level and increased risk of overall mortality. HbA1c > 6.6% was a negative prognostic factor for OS (HR: 1.593, 95% CI: 1.113-2.280, P=0.011). The median OS (95% CI) for nondiabetic patients, DM patients with HbA1c ≤6.6% and those with HbA1c > 6.6% was 22.22 (20.01-24.43), 25.28 (21.79-28.77) and 15.45 (7.57-23.33) months, respectively. Well-controlled DM patients had a comparable crude OS (HR (95% CI): 0.90 (0.76-1.08), P=0.273] compared to nondiabetic patients while patients with HbA1c>6.6% had a worse crude OS than patients without DM (HR (95% CI): 1.70 (1.24-2.34), P=0.001]. The survival benefit of good HbA1c control was prominent in all subgroups.
Conclusion: Impaired glycemic level negatively affects survival for patients with advanced NSCLC while proper glycemic control with HbA1c ≤6.6% improves the OS.

Keywords: diabetes; glycated hemoglobin A1C (HbA1C); glycemic control; non-small cell lung cancer; prognosis

DOI: https://doi.org/10.3389/fonc.2021.745150

Front Mol Biosci. 2021 ;8 757421

Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma.

Zili Dai, Taisheng Liu, Guihong Liu, Zhen Deng, Peng Yu, Baiyao Wang, Bohong Cen, Liyi Guo, Jian Zhang.

Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear. Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration. Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME. Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.

Keywords: hypoxia; immunity; lung cancer; overall survival; risk signature

DOI: https://doi.org/10.3389/fmolb.2021.757421