Association between Circulating Inflammatory Proteins and Clinical Prognosis in Chinese Patients with EGFR Mutation–Positive Non–Small Cell Lung Cancer

Guan, Rui; Lin, Anqi; Luo, Peng; Zhang, Jian

doi:10.1016/j.jtho.2019.05.027

Cited by 3 publications

(3 citation statements)

References 4 publications

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“…[ 10 ] Furthermore, FN1, KDR, PCNA , and TGFB1 interact in EGFR, VEGFA , and VEGFB -related subnetworks. [ 31 , 32 ] FOXP3 is a potential tumor suppressor gene, and TGFB1 can arrest the cell cycle in the G1–S phase to inhibit tumor cell proliferation. Consequently, in this study, the expression level of major genes that were antitumor treatment targets were compared among different immune subtypes.…”

Section: Discussionmentioning

confidence: 99%

Analysis of immune subtypes in non-small-cell lung cancer based on TCGA database

Chen

Song

2023

Medicine

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Immunotherapy is one of the main therapeutic approaches for non-small-cell lung cancer (NSCLC). Based on the poor response of immunotherapy, it is crucial to determine the most accurate and widespread predictive characteristics of NSCLC. We retrieved lung squamous cell carcinoma and lung adenocarcinoma gene expression profiles and clinical data from the cancer genome atlas database and classified them into 3 subtypes based on 29 immune gene sets. Combined with previous studies, the expression differences of related pathways and genes in different subtypes were analyzed. We classified them into 3 subtypes: Immunity High, Immunity Medium, and Immunity Low. Immunity High had the strongest immune cell infiltration and antitumor immune activity. Gene ontology enrichment analyses revealed enriched immune-related signaling pathways in lung squamous cell carcinoma. The hyperactivation of cancer-related pathways did not occur in any NSCLC. In addition, the Hippo signaling pathway was negatively correlated with immune signature, whereas epithelial-to-mesenchymal transition was positively correlated. In addition, we found significant differences in immune signatures between males and females; however, no correlation was observed with other clinical data. The identification of NSCLC subtypes based on immune signatures has potential clinical implications for NSCLC treatment.

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Section: Discussionmentioning

confidence: 99%

Analysis of immune subtypes in non-small-cell lung cancer based on TCGA database

Chen

Song

2023

Medicine

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“…About 75% are advanced (stage III–IV) at the time of diagnosis, and the 5-years survival rate is less than 20%. Non-small cell lung cancer (NSCLC) is the most common, accounting for 80–85% of all lung cancers, and about 57% of patients with advanced NSCLC have distant metastasis at the time of diagnosis ( Zappa and Mousa, 2016 ; Guan et al, 2019 ). Chemotherapy, targeted therapy, and anti-angiogenic drugs have become the cornerstone of treatment for these patients, but in recent years, the emergence of immune checkpoint inhibitors (ICIs) has changed the approach to NSCLC treatment.…”

Section: Introductionmentioning

confidence: 99%

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC

Wang

Liu²,

et al. 2022

Front. Pharmacol.

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Background: Lung cancer has the highest morbidity and mortality rate among types of malignant tumors, and as such, research into prolonging the survival time of patients is vital. The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC), however, the lack of effective biomarkers to predict the prognosis of immunotherapy has made it difficult to maximize the benefits. T cell receptor (TCR) is one of the most important components for recognizing tumor cells, and with this study we aim to clarify the relationship between TCR coexpression and the prognosis of NSCLC patients receiving immunotherapy.Methods: Univariate COX regression, logistics regression, and KM survival analysis were used to evaluate the relationship between TCR coexpression and the prognosis of immunotherapy. Additionally, CIBERSORT, Gene Set Enrichment Analysis (GSEA), and single-sample GSEA (ssGSEA) algorithms were used to evaluate the tumor immune microenvironment (TIME) of NSCLC patients.Results: Univariate Cox regression analysis showed that the TCR coexpression signature can be used as a clinical prognostic indicator for NSCLC patients receiving immunotherapy (p = 0.0205). In addition, those in the NSCLC group with a high TCR coexpression signature had significantly improved progression-free survival (PFS) (p = 0.014). In the ICI treatment cohort (GSE35640). In addition, there was a high infiltration of CD8+T cells, activated memory CD4+T cells, and M1 macrophages in the TIME of those with a high TCR coexpression signature. The results of pathway enrichment analysis showed that patients with a high TCR coexpression signature had significantly activated signal pathways such as lymphocyte proliferation and activation, chemokine binding, and inflammatory cytokine production. Also, we found that patients with a high TCR coexpression signature had an elevated T cell inflammation gene expression profile (GEP).Conclusion: We show that the TCR coexpression signature may be useful as a new biomarker for the prognosis of NSCLC patients undergoing immunotherapy, with high signatures indicating better treatment response. Additionally, we found that patients with a high TCR coexpression signature had tumor immune microenvironments with beneficial anti-tumor characteristics.

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“…These drugs fail to bind to original EGFR mutation sites and cause secondary mutations (5), resulting in primary drug resistance (6), secondary drug resistance (7), and activation of bypass pathway (8). It has been shown that tumour, node, metastasis (TNM) stage, tumor differentiation, serum laboratory indexes, or immunohistochemical (IHC) staining may be significant prognostic factors for NSCLC treated with EGFR-TKIs (9,10).…”

Section: Introductionmentioning

confidence: 99%

The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status

et al. 2021

Front. Med.

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Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial.Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots.Results: The expression levels of Ki-67 were divided into low (<60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P < 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P < 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes.Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.

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Association between Circulating Inflammatory Proteins and Clinical Prognosis in Chinese Patients with EGFR Mutation–Positive Non–Small Cell Lung Cancer

Cited by 3 publications

References 4 publications

Analysis of immune subtypes in non-small-cell lung cancer based on TCGA database

Analysis of immune subtypes in non-small-cell lung cancer based on TCGA database

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC

The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status

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