The key to immunotherapy: how to choose better therapeutic biomarkers for patients with non-small cell lung cancer

Pan, Yue; Fu, Yucheng; Zeng, Yue; Liu, Xiaohan; Peng, Yurong; Hu, Chunhong; Deng, Chao; Qiu, Zhenhua; Zou, Jianpeng; Liu, Yuxuan; Wu, Fang

doi:10.1186/s40364-022-00355-7

Cited by 34 publications

(28 citation statements)

References 119 publications

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“…Besides, patients with lower TMB and high-risk had worse prognosis. TMB is considered a potential biomarker for discriminating NSCLC patients who might benefit more from immunotherapy ( Pan et al, 2022 ). This also suggests that patients with high risk may be more sensitive to immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between necroptosis-related lncRNAs to construct a novel signature and predict the immune landscape of lung adenocarcinoma patients

Song

Zhao

et al. 2022

Front. Genet.

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Background: As a new style of cell death, necroptosis plays a crucial role in tumor immune microenvironment. LncRNAs have been identified to act as competitive RNAs to influence genes involved in necroptosis. Therefore, we aim to create a signature based on necroptosis-related lncRNAs to predict the prognosis and immune landscape of lung adenocarcinoma (LUAD) patients in this study.Methods: TCGA database was used to acquire RNA sequencing (RNA-Seq) data and clinical information for 59 lung normal samples and 535 lung adenocarcinoma samples. The Pearson correlation analysis, univariate cox regression analysis and least absolute shrinkage and selection operator (LASSO) cox regression were performed to construct the prognostic NRlncRNAs signature. Then we used Kaplan-Meier (K-M) analysis, timedependent ROC curves, univariate and multivariate cox regression analysis, and nomogram to validate this signature. In addition, GO, KEGG, and GSVA were analyzed to investigate the potential molecular mechanism. Moreover, we analyzed the relationship between our identified signature and immune microenvironment, TMB, and some clinical characteristics. Finally, we detected the expression of the six necroptosis-related lncRNAs in cells and tissues.Results: We constructed a NRlncRNAs signature consisting of six lncRNAs (FRMD6-AS1, LINC01480, FAM83A-AS1, FRMD6-AS1, MED4-AS1, and LINC01415) in LUAD. LUAD patients with high risk scores had lower chance

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Section: Discussionmentioning

confidence: 99%

Cross-talk between necroptosis-related lncRNAs to construct a novel signature and predict the immune landscape of lung adenocarcinoma patients

Song

Zhao

et al. 2022

Front. Genet.

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“…There are many studies examining whether genetic mutations affect the efficacy of immunotherapy and patients' survival [4]. Because integrated genomic analysis is not currently practical in the clinical setting, there has been considerable interest in developing LRP2 mutation signature.…”

Section: Development and Validation Of A Prognostically Lrp2 Mutant S...mentioning

confidence: 99%

“…To date, the FDA has approved PD-1, defective mismatch repair or microsatellite instability high (dMMR/MSI-H), and tumor mutation burden (TMB) to predict response to immunotherapy [3]. In addition, several genomic alterations, such as TP53, KRAS, KMT2C, CDKN2A/CDKN2B and MDM2/MDM4, have been reported to occur in tumors that are highly responsive to ICIs [4]. However, due to the complex interplay between tumor cells, tumor microenvironments (TME), and host immunity, new predictive markers for individual immunotherapy remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

Integrated in silico analysis of LRP2 mutations to immunotherapy efficacy in pan-cancer cohort

Ding

Zhang

et al. 2022

Discov Onc

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Purpose Immunotherapy has emerged as a novel therapy, while many patients are refractory. Although, several biomarkers have been identified as predictive biomarkers for immunotherapy, such as tumor specific genes, PD-1/PD-L1, tumor mutation burn (TMB), and microsatellite instability (MSI), results remain unsatisfactory. The aim of this study is to evaluate the value of LRP2 mutations in predicating cancer immunotherapy. Methods We investigated the characteristics of low-density lipoprotein receptor-related protein 2 (LRP2) mutation in the cancer genome atlas (TCGA) and explored the potential association of LRP2 mutations with immunotherapy. Characteristics of LRP2 mutations in 33 cancer types were analyzed using large-scale public data. The association of LRP2 mutations with immune cell infiltration and immunotherapy efficacy was evaluated. Finally, a LPR2 mutation signature (LMS) was developed and validated by TCGA-UCEC and pan-cancer cohorts. Furthermore, we demonstrated the predictive power of LMS score in independent immunotherapy cohorts by performing a meta-analysis. Results Our results revealed that patients with LRP2 mutant had higher TMB and MSI compared with patients without LRP2 mutations. LRP2 mutations were associated with high levels of immune cells infiltration, immune-related genes expression and enrichment of immune related signaling pathways. Importantly, LRP2-mutated patients had a long overall survival (OS) after immunotherapy. In the endometrial cancer (EC) cohort, we found that patients with LRP2 mutations belonged to the POLE and MSI-H type and had a better prognosis. Finally, we developed a LRP2 mutations signature (LMS), that was significantly associated with prognosis in patients receiving immunotherapy. Conclusion These results indicated that LRP2 mutations can serve as a biomarker for personalized tumor immunotherapy. Importantly, LMS is a potential predictor of patients’ prognosis after immunotherapy.

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“…TMB is defined as the number of total mutations in the tumor and is the most common predictor of response to ICIs after anti-PD-L1 immunohistochemistry staining in the USA [ 135 ]. However, it is debatable which mutations trigger the immunogenicity by neoantigen [ 125 ]; thus, the expression of PD-L1 on NSCLC cells remains a key clinical biomarker of responsiveness to ICIs [ 136 ]. Despite many advantages of ICIs, NSCLC patients respond differently to immunocompetent agents: 10–15% of NSCLC patients show a very long-term response (longer than 5 years), 40–50% of patients indicate a primary resistance, and 25–35% of patients acquire the resistance within the first 6–12 months of treatment [ 137 ].…”

Section: Role Of Liquid Biopsy In the Monitoring Of Response To Perso...mentioning

confidence: 99%

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

Bożyk

Nicoś

2022

Life

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The standard diagnostics procedure for non-small-cell lung cancer (NSCLC) requires a pathological evaluation of tissue samples obtained by surgery or biopsy, which are considered invasive sampling procedures. Due to this fact, re-sampling of the primary tumor at the moment of progression is limited and depends on the patient’s condition, even if it could reveal a mechanism of resistance to applied therapy. Recently, many studies have indicated that liquid biopsy could be provided for the noninvasive management of NSCLC patients who receive molecularly targeted therapies or immunotherapy. The liquid biopsy of neoplastic patients harbors small fragments of circulating-free DNA (cfDNA) and cell-free RNA (cfRNA) secreted to the circulation from normal cells, as well as a subset of tumor-derived circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA). In NSCLC patients, a longitudinal assessment of genetic alterations in “druggable” genes in liquid biopsy might improve the follow-up of treatment efficacy and allow for the detection of an early progression before it is detectable in computed tomography or a clinical image. However, a liquid biopsy may be used to determine a variety of relevant molecular or genetic information for understanding tumor biology and its evolutionary trajectories. Thus, liquid biopsy is currently associated with greater hope for common diagnostic and clinical applications. In this review, we would like to highlight diagnostic challenges in the application of liquid biopsy into the clinical routine and indicate its implications on the metastatic spread of NSCLC or monitoring of personalized treatment regimens.

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The key to immunotherapy: how to choose better therapeutic biomarkers for patients with non-small cell lung cancer

Cited by 34 publications

References 119 publications

Cross-talk between necroptosis-related lncRNAs to construct a novel signature and predict the immune landscape of lung adenocarcinoma patients

Cross-talk between necroptosis-related lncRNAs to construct a novel signature and predict the immune landscape of lung adenocarcinoma patients

Integrated in silico analysis of LRP2 mutations to immunotherapy efficacy in pan-cancer cohort

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

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