Proteomic Analyses Identify Differentially Expressed Proteins and Pathways Between Low-Risk and High-Risk Subtypes of Early-Stage Lung Adenocarcinoma and Their Prognostic Impacts

Zhou, Juntuo; Liu, Bing; Li, Zhongwu; Li, Yang; Chen, Xi; Ma, Yuanyuan; Shi, Yan; Yang, Xin; Zhong, Liang; Wu, Nan

doi:10.1074/mcp.ra120.002384

Cited by 12 publications

(7 citation statements)

References 36 publications

(42 reference statements)

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“…Moreover, high-expression ERO1A in cancers pertains to tumor cell migration and proliferation [ 18 , 22 , 40 ]. Meanwhile, ERO1A overexpression was associated with poor prognosis [ 19 , 37 ] that coincides exactly with our data. Afterward, functional experiment denoted that miR-218-5p constrained LUAD cell functions through inhibiting ERO1A expression.…”

Section: Discussionsupporting

confidence: 91%

“…Endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) is an oxidortase in the endoplasmic reticulum and the primary regulator of protein disulfide isomerase (PDI) oxidation [ 14 , 15 ]. The overexpression of ERO1A in cancers, like breast cancer [ 16 ], gastric cancer [ 17 ], pancreatic cancer [ 18 ], and LUAD [ 19 ], is linked with poor prognoses of patients. Besides, ERO1A upregulation induces vascular endothelial growth factor (VEGF) expression and angiogenesis [ 20–22 ].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha

Chen

Wang

2022

Bioengineered

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Lung adenocarcinoma (LUAD) severely threatens the health of people owing to its lethality. Nonetheless, the underlying mechanisms on LUAD development remain unclear to a great extent. This work aimed to probe the functions of miR-218-5p in LUAD. MiR-218-5p and endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) were screened as differently downregulated and upregulated RNAs in LUAD, respectively, by bioinformatics analyses. The results of cell functional assays stated that enforced expression of miR-218-5p notably restrained cell viability, invasion, and migration in LUAD. MiR-218-5p may interact with 3’-untranslated region of ERO1A mRNA as analyzed by bioinformatics. Afterward, western blot and dual-luciferase reporter gene analyses were introduced to identify their interaction. ERO1A overexpression reversed the suppressive impacts of miR-218-5p on LUAD cell progression, indicating the implication of miR-218-5p/ERO1A axis in suppressing cancer development. We also observed that this regulatory axis suppressed angiogenesis in LUAD. Taken together, miR-218-5p/ERO1A axis exerted an imperative role in LUAD cell progression, which provides a valuable clue for the development of LUAD therapeutic regimen.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha

Chen

Wang

2022

Bioengineered

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“…According to the 2015 World Health Organization Classification of Lung Cancer (3), based on prognosis, lung adenocarcinoma is classified into five histopathological subtypes. Micropapillary type is a high-risk subtype which has the potential for rapid metastasis and a poor prognosis (4,5). Micropapillary pattern (MPP) refers to the free central cluster of cells lacking fibrous vessels (6).…”

Section: Introductionmentioning

confidence: 99%

Enhanced CT-Based Radiomics to Predict Micropapillary Pattern Within Lung Invasive Adenocarcinoma

Hou

et al. 2021

Front. Oncol.

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ObjectiveWe aimed to investigate whether enhanced CT-based radiomics can predict micropapillary pattern (MPP) of lung invasive adenocarcinoma (IAC) in the pre-op phase and to develop an individual diagnostic predictive model for MPP in IAC.Methods170 patients who underwent complete resection for pathologically confirmed lung IAC were included in our study. Of these 121 were used as a training cohort and the other 49 as a test cohort. Clinical features and enhanced CT images were collected and assessed. Quantitative CT analysis was performed based on feature types including first order, shape, gray-level co-occurrence matrix-based, gray-level size zone matrix-based, gray-level run length matrix-based, gray-level dependence matrix-based, neighboring gray tone difference matrix-based features and transform types including Log, wavelet and local binary pattern. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to value the ability to identify the lung IAC with MPP using these characteristics.ResultsUsing quantitative CT analysis, one thousand three hundred and seventeen radiomics features were deciphered from R (https://www.r-project.org/). Then these radiomic features were decreased to 14 features after dimension reduction using the least absolute shrinkage and selection operator (LASSO) method in R. After correlation analysis, 5 key features were obtained and used as signatures for predicting MPP within IAC. The individualized prediction model which included age, smoking, family tumor history and radiomics signature had better identification (AUC=0.739) in comparison with the model consisting only of radiomics features (AUC=0.722). DeLong test showed that the difference in AUC between the two models was statistically significant (P<0.01). Compared with the simple radiomics model, the more comprehensive individual prediction model has better prediction performance.ConclusionThe use of radiomics approach is of great value in the diagnosis of tumors by non-invasive means. The individualized prediction model in the study, when incorporated with age, smoking and radiomics signature, had effective predictive performance of lung IAC with MPP lesions. The combination of imaging features and clinical features can provide additional diagnostic value to identify the micropapillary pattern in IAC and can affect clinical diagnosis and treatment.

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“…Zhang et al compared the transcriptomic profiles between SPA and acinar predominant adenocarcinoma and showed that SPA was enriched in pathways associated with RNA polymerase activity and p53 inactivation (7). Zhou et al performed comprehensive proteomic analyses of high-risk LUAD subtypes (micropapillary and solid) and low-risk subtype (lepidic) and found that differentially expressed proteins were enriched in pathways involved in remodeling of extracellular matrix and activation of DNA replication and cell cycle (8). Dong et al investigated the immune profiles of LUAD histologic subtypes and discovered that SPA was correlated with an immunoresistant tumor microenvironment (3).…”

Section: Introductionmentioning

confidence: 99%

Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma

Wang²,

Wang³

et al. 2023

Front. Immunol.

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BackgroundSolid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.MethodsWe conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.ResultsAlong with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.ConclusionsCompared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.

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Proteomic Analyses Identify Differentially Expressed Proteins and Pathways Between Low-Risk and High-Risk Subtypes of Early-Stage Lung Adenocarcinoma and Their Prognostic Impacts

Cited by 12 publications

References 36 publications

MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha

MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha

Enhanced CT-Based Radiomics to Predict Micropapillary Pattern Within Lung Invasive Adenocarcinoma

Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma

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