bims-meluca 2023-01-01 papers

Nutr Cancer. 2022 Dec 27. 1-10

The Effect of Body Mass Index on Survival in Lung Cancer.

Fatma Yağmur Evcil, Özgür Önal, Emine Elif Özkan.

The prognostic significance of body mass index in lung cancer and the direction of this relationship are not yet clear. This study aimed to evaluate the relationship between BMI and overall survival time of advanced-stage lung cancer patients treated in a center in Turkey, a developing country. In this study, the data of 225 patients diagnosed with stage III or stage IV lung cancer between 2016 and 2020 were analyzed. The effects of BMI and other variables on survival were examined by Cox regression analysis for NSCLC and SCLC. For NSCLC and SCLC, being underweight compared to the normal group, being diagnosed at a more advanced stage, and having a worse performance score were associated with a significantly higher risk of death. Other variables significantly associated with survival were gender, type of radiotherapy for NSCLC, age group, and family history for SCLC. This study showed that being underweight relative to the normal group was associated with worse survival for NSCLC and SCLC but did not support the obesity paradox. Studies that are representative of all BMI categories and free of bias are needed to understand the BMI-lung cancer survival relationship clearly.

DOI: https://doi.org/10.1080/01635581.2022.2159045

Biomed Res Int. 2022 ;2022 6405228

Prognostic Biomarkers after Radiotherapy for Nonsmall Cell Lung Cancer Based on Bioinformatics Analysis.

Kejun Li, Shuang Wang, Na Li, Wenyue Zhao, Ningning He, Jinhan Wang, Kaihua Ji, Manman Zhang, Huijuan Song, Qiang Liu, Liqing Du.

Radiotherapy is one of the main treatment modalities in nonsmall cell lung cancer (NSCLC). However, tumor radiosensitivity is influenced by intrinsic factors like genetic variations and extrinsic factors like tumor microenvironment. Consequently, we hope to develop novel biomarkers, so as to improve the response rate of radiotherapy and overcome resistance to radiotherapy in NSCLC. We investigate the difference genes of primary NSCLC patients before and after radiotherapy in GSE162945 dataset. Gene Ontology (GO), KEGG, Reactome, and GSEA were employed to represent the essential gene and biological function. It was found that most pathway genes clustered in extracellular matrix and ECM-receptor signal pathway. Additionally, TMT-based proteomics was used to survey the differential proteins present in the supernatant of H460 cells before or after irradiation with 2 Gy of γ-rays. And then we take the intersection between the proteomics of H460 cell and ECM-receptor signal pathway proteins of GSE162945 datasets. The data revealed that fibronectin 1 (FN1) and thrombin reactive protein 1 (THBS1) were upregulated after radiation in both datasets. Subsequently, survival analyses using the GEPIA web server demonstrated that FN1 and THBS1 had significant prognostic values (Logrank test P value < 0.05) for LUAD and LUSC. Our observations from this study suggest that FN1 and THBS1 might have potential to serve as novel biomarkers for predicting NSCLC tumor response to radiotherapy.

DOI: https://doi.org/10.1155/2022/6405228

J Clin Lab Anal. 2022 Dec 26. e24824

LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma.

Shan Wang, Zhaoxin Chen, Hongwei Lv, Cong Wang, Huamin Wei, Jing Yu.

BACKGROUND: Although many biomarkers for lung adenocarcinoma (LUAD) have been identified, their specificity and sensitivity remain unsatisfactory. Endothelial lipase gene (LIPG) plays an important role in a variety of cancers, but its role in lung adenocarcinoma remains unclear.
METHODS: TCGA, GEO, K-M plotter, CIBERSORT, GSEA, HPA, and GDSC were used to analyze LIPG in LUAD. Data analysis was mainly achieved by R 4.0.3.
RESULTS: The expression of LIPG in LUAD tissues was higher than that in adjacent normal tissues, especially in women, patients aged >65 years, and those with lymph node metastasis. High expression predicted a poor prognosis. The results of enrichment analysis suggest that LIPG may exert profound effects on the development of LUAD through multiple stages of lipid metabolism and immune system regulation. In addition, LIPG expression was significantly correlated with the expression levels of multiple immune checkpoint genes and the abundance of multiple immune infiltrates, including the activated memory CD4 T cell, M1 macrophage, neutrophil, plasma cells, and T follicular helper (Tfh) cells in the LUAD microenvironment content. At the same time, patients with high LIPG expression respond well to a variety of antitumor drugs and have a low rate of drug resistance.
CONCLUSIONS: LIPG is a prognostic marker and is associated with lipid metabolism and immune infiltration in LUAD.

Keywords: LIPG ; biomarker; immune checkpoint blocker; immune infiltrates; lung adenocarcinoma

DOI: https://doi.org/10.1002/jcla.24824

Metabolomics. 2022 Dec 27. 19(1): 3

Untargeted metabolomics and lipidomics identified four subtypes of small cell lung cancer.

Chenyue Zhang, Xiaoling Shang, Haiyong Wang.

INTRODUCTION: Small cell lung cancer (SCLC) is a heterogeneous malignancy with dismal prognosis. However, few studies have conducted on the metabolic heterogeneity in SCLC.
OBJECTIVE: We therefore identify SCLC classifications using untargeted metabolomics and lipidomics. We also compared their survival and the immunotherapy responses.
METHODS: Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis was performed in 191 SCLC serum samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to identify metabolic pathways. The Kaplan-Meier and log-rank test were used to analyze the survival curves. The univariate and multivariate Cox proportional hazards regression models were used to evaluate prognostic factors for OS in patients with SCLC.
RESULTS: Distinct subtypes of SCLC were identified by consensus clustering algorithm using partioning around medoids (pam) based on untargeted metabolomics and lipidomics. Four distinct subtypes of SCLC were identified, with distinct metabolic pathways. Subgroup 2 had the longest survival whereas Subgroup 1 had the shortest. Subtype 2 benefited most from immunotherapy in OS, as in contrast to Subtype 3 with shortest survival.
CONCLUSION: Our study revealed the metabolic heterogeneity in SCLC and identified four subtypes with distinct metabolic features. It indicates promising therapeutic and prognostic value that may guide treatment for SCLC. The subtype-specific clinical trials may be designed and would be instructive for drug development.

Keywords: Lipidomics; Metabolic subtype; Small cell lung cancer; Untargeted metabolomics

DOI: https://doi.org/10.1007/s11306-022-01964-x

Front Immunol. 2022 ;13 1059995

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study.

Shubin Chen, Haowen Wei, Wenhua Zhao, Wei Jiang, Ruiling Ning, Shaozhang Zhou, Liping Tan, Huilin Wang, Cuiyun Su, Jianbo He, Aiping Zeng, Yun Zhao, Qitao Yu.

Background: The aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer.
Methods: In this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents' group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox's proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis.
Results: The average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group.
Conclusion: PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.

Keywords: PD-1/PD-L1 inhibitors; advanced non-small cell lung cancer; anti-angiogenic agents; real-world study; second or later-line therapy

DOI: https://doi.org/10.3389/fimmu.2022.1059995

Eur J Hybrid Imaging. 2022 Dec 28. 6(1): 37

Volumetric parameters of the primary tumor and whole-body tumor burden derived from baseline 18F-FDG PET/CT can predict overall survival in non-small cell lung cancer patients: initial results from a single institution.

Hemat A Mahmoud, Walaa Oteify, Hussein Elkhayat, Ahmed M Zaher, Taha Zaki Mohran, Nesreen Mekkawy.

BACKGROUND: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters derived from 18F-FDG PET/CT, suggested to have a prognostic value in cancer patients. Our study aimed to test whether these volumetric parameters of the primary tumor and whole-body tumor burden (WBTB) can predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients.
MATERIALS AND METHODS: Thirty biopsy-proven NSCLC patients who had not begun anti-tumor therapy were included in this prospective study. A baseline 18F-FDG PET/CT study was acquired. Scans were interpreted visually and semi-quantitatively by drawing a 3D volume of interest (VOI) over the primary tumor and all positive lesions to calculate metabolic, volumetric parameters, and WBTB. The PET parameters were used to stratify patients into high- and low-risk categories. The overall survival was estimated from the date of scanning until the date of death or last follow-up.
RESULTS: At a median follow-up of 22.73 months, the mean OS was shorter among patients with higher tu MTV and tu TLG and high WBTB. High WB TLG was independently associated with the risk of death (p < 0.025). Other parameters, e.g., SUVmax, SUVpeak, and SUVmean, were not predictive of outcomes in these patients.
CONCLUSION: In patients with NSCLC, tu MTV, tu TLG, and WBTB determined on initial staging 18F-FDG PET/CT seems to be a strong, independent imaging biomarker to predict OS, superior to the clinical assessment of the primary tumor. The WB TLG was found to be the best predictor of OS.

Keywords: 18F-FDG PET/CT; Non-small cell lung cancer; Overall survival; Whole-body tumor burden

DOI: https://doi.org/10.1186/s41824-022-00158-x