bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2022–12–11
seven papers selected by
the Muñoz-Pinedo/Nadal (PReTT) lab, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Modulation of heme and tumor vascular oxygenation- a novel strategy for lung cancer therapy.
  2. Role of 18F-FDG PET/CT and sarcopenia in untreated non-small cell lung cancer with advanced stage.
  3. The amino acid and carnitine concentration changes in bronchoalveolar lavage fluid from lung cancer patients.
  4. Plasma GDF15 levels associated with circulating immune cells predict the efficacy of PD-1/PD-L1 inhibitor treatment and prognosis in patients with advanced non-small cell lung cancer.
  5. Hypoxia-associated prognostic markers and competing endogenous RNA coexpression networks in lung adenocarcinoma.
  6. Identification of a novel oxidative stress-related prognostic model in lung adenocarcinoma.
  7. The Effect of Nutritional Support Based on the Dietary Anti-Inflammatory Index on Cancer-Related Fatigue in Lung Cancer Patients Undergoing Chemotherapy.
  1. Oncoscience. 2022 ;9 66-69
    Modulation of heme and tumor vascular oxygenation- a novel strategy for lung cancer therapy.
    Poorva Ghosh, Ralph P Mason, Li Liu, Li Zhang.
      Hypoxia and faulty vasculature are well-known hallmarks of cancer and in addition to being associated with poor prognosis in patients, these hallmarks are also known to contribute to therapy resistance. In recent years, therapeutics that alleviate hypoxia and promote normalization of vasculature are being explored for cancer therapy. In addition to being hypoxic, cancers such as non-small cell lung cancers exhibit elevated oxidative phosphorylation. Therapeutic strategies that can normalize vasculature and reduce oxidative phosphorylation could greatly benefit the landscape of cancer therapeutics. Here, we highlight a heme-targeting therapeutic strategy that demonstrates significant tumor growth inhibition in non-small cell lung cancer mouse models using multi-spectral optoacoustic tomography.
    Keywords:  heme; lung cancer; tumor vascular oxygenation
    DOI:  https://doi.org/10.18632/oncoscience.569
  2. Jpn J Radiol. 2022 Dec 08.
    Role of 18F-FDG PET/CT and sarcopenia in untreated non-small cell lung cancer with advanced stage.
    Hui Yuan, Xiaoyue Tan, Xiaolin Sun, Li He, Dongjiang Li, Lei Jiang.
       BACKGROUND: Sarcopenia is essential in managing advanced stage (III-IV) non-small cell lung cancer (NSCLC) but is laborious to diagnose using currently available method. This study aimed to establish a simple approach to predict sarcopenia using 18F-FDG PET/CT parameters and clinical characteristics and determine their roles in prognostication in advanced stage NSCLC.
    METHODS: Untreated 202 NSCLC patients with stage III-IV were retrospectively reviewed. Sarcopenia was defined using the skeletal muscle index (SMI) measured at the third lumbar vertebra (L3). 18F-FDG PET/CT metabolic parameters of maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis of the primary tumor (SUVmax_T, MTV_T, and TLG_T) and of whole-body lesions (MTV_WB and TLG_WB) were measured. Besides, SUVmax of the psoas major muscle (SUVmax_Muscle) was measured at the L3 level. The diagnostic endpoint was the probability of sarcopenia, and the survival endpoints included progression-free survival (PFS) and overall survival (OS).
    RESULTS: Among the enrolled 202 patients, 82 (40.6%) were diagnosed with sarcopenia. Higher age, male, lower BMI, and lower SUVmax_Muscle were correlated with a higher incidence of sarcopenia (P < 0.05), while age, sex, BMI, and SUVmax_Muscle were independently predictive of sarcopenia, and thus were utilized to construct a nomogram model. Multivariate Cox regression analysis revealed that sarcopenia score derived from the nomogram model, sarcopenia, stage, and TLG_WB were independently predictive of both PFS and OS.
    CONCLUSION: The incidence of sarcopenia increased with declining SUVmax_Muscle in advanced stage NSCLC. Our model using age, sex, BMI, and SUVmax_Muscle might be substituted for the complicated measurement of SMI. After adjustment by stage and TLG_WB, both sarcopenia score and sarcopenia were found to be independently predictive of PFS and OS.
    Keywords:  18F-FDG PET/CT; Advanced stage; Non-small cell lung cancer (NSCLC); Prognosis; Sarcopenia
    DOI:  https://doi.org/10.1007/s11604-022-01369-9
  3. World J Surg Oncol. 2022 Dec 04. 20(1): 380
    The amino acid and carnitine concentration changes in bronchoalveolar lavage fluid from lung cancer patients.
    Xiaojun Sun, Mengmin Xu, Liren Ding, Guobiao Yang, Jianlong Kong, Yafang Zhu, Xuefang Chen, Liang Xu, Yisha Shan, Yupin Xu.
       OBJECTIVE: To screen out potential biomarkers by analyzing fundamental nutrients in the bronchoalveolar lavage fluid (BALF) before confirming the lung cancer.
    METHODS: In this study, 44 patients were enrolled with clinical information. The concentrations of 23 amino acids and 35 carnitines in their BALF were detected with the high-performance liquid chromatography-mass spectrometry (HPLC-MS). Combined with clinicopathological diagnosis, the patients were divided into the lung cancer group (grades I & II and III & IV) and the non-cancer group for standard statistical analysis.
    RESULTS: The partial least squares-discriminant analysis (PLS-DA), the Shapiro-Wilk test, and the Bonferroni correction results showed that the serine concentration was higher and the butane-diacyl-carnitine (C4DC) concentration was lower in the lung cancer group, further showing the same changing trend continuously through the non-cancer stage, grades I & II stage and grades III & IV stage. Those two potential biomarkers have been identified.
    CONCLUSION: The HPLC-MS target detection in clinic for nutrient concentration levels is a promising technique to find the changing concentration of serine and C4DC in BALF, which provides an economical and practical way for early warning of lung cancer.
    Keywords:  BALF; Biomarker; Lung cancer; Targeted metabolomics
    DOI:  https://doi.org/10.1186/s12957-022-02850-5
  4. J Cancer Res Clin Oncol. 2022 Dec 06.
    Plasma GDF15 levels associated with circulating immune cells predict the efficacy of PD-1/PD-L1 inhibitor treatment and prognosis in patients with advanced non-small cell lung cancer.
    Green Hong, Pureum Sun, Chaeuk Chung, Dongil Park, Song-I Lee, Nayoung Kim, Seong Eun Lee, Jeong Eun Lee, Yea Eun Kang, Da Hyun Kang.
       PURPOSE: Although increased plasma growth differentiation factor-15 (GDF15) levels have been reported in patients with various cancers, the predictive role of PD-1/PD-L1 inhibitors in advanced cancers remains unknown. This study aimed to investigate GDF15 levels as a predictive marker in advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors and analyze their association with immune cell populations.
    METHODS: This study included 87 patients with advanced NSCLC receiving anti-PD-1/PD-L1 inhibitors between March 2018 and May 2020. Blood samples were obtained immediately before and months after PD-1/PD-L1 inhibitor administration.
    RESULTS: The objective response rate (ORR) was significantly higher in the low GDF15 than in the high GDF15 group (39.2% vs. 15.3%, P = 0.013). The median progression-free survival (PFS) was significantly longer in the low GDF15 than in the high GDF15 group (13.2 [95% CI 7.6-18.9] vs. 7.2 [95% CI 4.8-9.6] months, P = 0.048). Moreover, plasma GDF15 levels negatively correlated with PD-1+/CD8+ T cells (r = - 0.399, P = 0.003) and positively with PD-1+/Treg cells (r = 0.507, P < 0.001) and PD-1+Treg/CD4+ T cells (r = 0.439, P < 0.001). The ORR was significantly higher in the group with decreased GDF15 from baseline than in the increased GDF15 group (37.2% vs. 10.0%, P = 0.026). The median PFS was significantly longer in the decreased GDF15 group (14.8 [95% CI 10.4-19.2] vs. 5.9 [95% CI 2.8-9.0] months, P = 0.002). Plasma GDF15 levels were associated with PD-1+CD8+ T cells and PD-1+ Treg cells.
    CONCLUSION: Plasma GDF15 could be a potential biomarker for predicting the efficacy and survival benefit of immunotherapy in advanced NSCLC.
    Keywords:  Biomarker; Efficacy; GDF15; Immunotherapy; Non-small cell lung cancer; Survival
    DOI:  https://doi.org/10.1007/s00432-022-04500-5
  5. Sci Rep. 2022 Dec 09. 12(1): 21340
    Hypoxia-associated prognostic markers and competing endogenous RNA coexpression networks in lung adenocarcinoma.
    Lecai Xiong, Xueyu He, Le Wang, Peng Dai, Jinping Zhao, Xuefeng Zhou, Hexiao Tang.
      Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC). Hypoxia has been found in 50-60% of locally advanced solid tumors and is associated with poor prognosis in various tumors, including NSCLC. This study focused on hypoxia-associated molecular hallmarks in LUAD. Fifteen hypoxia-related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on data from The Cancer Genome Atlas (TCGA). Then, we investigated the immune status under different hypoxia statuses. Subsequently, we constructed prognostic models based on hypoxia-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNA (ceRNA) theory. Two clusters (Cluster 1 and Cluster 2) were identified with different hypoxia statuses. Cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4+ T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB scores were higher in Cluster 1, indicating an immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated with prognosis under different hypoxia clusters and their related mRNAs and lncRNAs were identified, and a ceRNA network was built. This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of the gene signature and ceRNA theory.
    DOI:  https://doi.org/10.1038/s41598-022-25745-7
  6. Front Pharmacol. 2022 ;13 1030062
    Identification of a novel oxidative stress-related prognostic model in lung adenocarcinoma.
    Yifan Zhu, Quanying Tang, Weibo Cao, Ning Zhou, Xin Jin, Zuoqing Song, Lingling Zu, Song Xu.
      Background: Oxidative stress (OxS) participates in a variety of biological processes, and is considered to be related to the occurrence and progression of many tumors; however, the potential diagnostic value of OxS in lung cancer remains unclear. Methods: The clinicopathological and transcriptome data for lung adenocarcinoma (LUAD) were collected from TCGA and GEO database. LASSO regression was used to construct a prognostic risk model. The prognostic significance of the OxS-related genes was explored using a Kaplan-Meier plotter database. The prediction performance of the risk model was shown in both the TCGA and GSE68465 cohorts. The qRT-PCR was performed to explore the expression of genes. CCK-8, Edu and transwell assays were conducted to analyze the role of CAT on cell proliferation migration and invasion in lung cancer. Immune infiltration was evaluated by CIBERSORT and mutational landscape was displayed in the TCGA database. Moreover, the relationship between risk score with drug sensitivity was investigated by pRRophetic. Results: We identified a prognosis related risk model based on a four OxS gene signature in LUAD, including CYP2D6, FM O 3, CAT, and GAPDH. The survival analysis and ROC curve indicated good predictive power of the model in both the TCGA and GEO cohorts. LUAD patients in the high-risk group had a shorter OS compared to the low-risk group. QRT-PCR result showed that the expression of four genes was consistent with previous analysis in cell lines. Moreover, overexpression of CAT could decrease the proliferation, invasion and migration of lung cancer cells. The Cox regression analysis showed that the risk score could be used as an independent prognostic factor for OS. LUAD patients in the high-risk score group exhibited a higher tumor mutation burden and risk score were closely related to tumor associated immune cell infiltration, as well as the expression of immune checkpoint molecules. Both the high- and low-risk groups have significant differences in sensitivity to some common chemotherapy drugs, such as Paclitaxel, Docetaxel, and Vinblastine, which may contribute to clinical treatment decisions. Conclusion: We established a robust OxS-related prognostic model, which may contribute to individualized immunotherapeutic strategies in LUAD.
    Keywords:  LUAD; drug response; immune infiltration; nomogram; oxidative stress
    DOI:  https://doi.org/10.3389/fphar.2022.1030062
  7. Cancer Nurs. 2022 Dec 01.
    The Effect of Nutritional Support Based on the Dietary Anti-Inflammatory Index on Cancer-Related Fatigue in Lung Cancer Patients Undergoing Chemotherapy.
    Yanmei Zhang, Guanjun Cui, Yang Xiu, Mei Zhao.
       BACKGROUND: Cancer-related fatigue is one of the most common symptoms reported by cancer patients and is considered to be related to inflammation.
    OBJECTIVE: This study aimed to explore the effects of nutritional support based on the dietary anti-inflammatory index on cancer-related fatigue in lung cancer patients undergoing chemotherapy.
    METHODS: This was a randomized controlled trial with 106 lung cancer patients who were divided into either the anti-inflammatory diet group (n = 53) or the usual diet group (n = 53) for 3 months. The primary outcome was cancer-related fatigue. Secondary outcomes included high sensitivity C-reactive protein (hs-CRP) concentrations, nutritional status, and quality of life. Repeated-measures analysis of variance was used to examine the effectiveness of this intervention.
    RESULTS: The anti-inflammatory diet improved fatigue (-1.99 ± 1.78, P < .001), hs-CRP levels (-4.15 [-11.87, -0.58], P < .001), Patient-Generated Subjective Global Assessment (-2.53 ± 3.11, P = .030), and albumin concentrations (2.83 ± 0.59, P < .001) compared with the usual diet after 3 months. Simultaneously, in the repeated-measures analysis of variance, the differences in fatigue (F = 5.536, P < .001), hs-CRP levels (F = 6.918, P < .001), and albumin concentrations (F = 2.727, P = .048) were statistically significant for the group-by-time interaction.
    CONCLUSION: The study provided evidence for the positive effect of nutritional support based on the dietary anti-inflammatory index on cancer-related fatigue, hs-CRP levels, nutritional status, and quality of life in lung cancer patients undergoing chemotherapy.
    IMPLICATION FOR PRACTICE: With an anti-inflammatory diet, nurses can help these patients improve their overall quality of life.
    DOI:  https://doi.org/10.1097/NCC.0000000000001124
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