Association between PD-L1 expression and driver gene mutations in non-small cell lung cancer patients: correlation with clinical data

Karatrasoglou, Eleni A.; Chatziandreou, Ilenia; Sakellariou, Stratigoula; Stamopoulos, Konstantinos; Kavantzas, Nikolaos; Lazaris, Andreas C.; Korkolopoulou, Penelope; Saetta, Angelica A.

doi:10.1007/s00428-020-02756-1

Cited by 24 publications

(20 citation statements)

References 50 publications

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“…Regarding LUAD's targeted treatment strategies, such as EGFR KRAS, ALK, etc., druggable genetic alterations are crucial for their correlation with clinical and pathological features. These decisions about therapeutic strategies affect the prognosis of lung adenocarcinoma patients [32][33][34]. For example, EGFR and KRAS mutated LUADs have a dramatic prognosis among non-smokers and smokers.…”

Section: Discussionmentioning

confidence: 99%

mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers

Zhang

Tseng

Lien

et al. 2020

Genes

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Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.

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Section: Discussionmentioning

confidence: 99%

mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers

Zhang

Tseng

Lien

et al. 2020

Genes

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“…Previous reports only consistently shown that KRAS mutations are positively correlated with PD-L1 expression, while the relationship between other gene mutation status and PD-L1 expression shown inconsistent conclusions. [26] Therefore, in clinical practice, it is meaningful to pay more attention to rare mutations in male patients with adenocarcinoma. Also, for patients with rare mutations, further detection of PD-L1 expression level will have more hints for clinical treatment.…”

Section: Discussionmentioning

confidence: 99%

Pathological Signature and Therapeutic Status of NSCLC Patients with Common or Rare Driver Gene Alterations in North China：A real world retrospective study

Zhang

Yang

et al. 2020

Preprint

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Background: Although guidelines recommended to test EGFR/ALK/ROS-1 gene alterations in advanced non-small cell lung cancer (NSCLC) patients before treatment, there is now growing evidence that rare driver genes and mutations also can inform targeted therapy and improve outcomes for this traditionally underrepresented population. This study aimed to describe mutational patterns and linked clinical parameters in a Chinese population-based NSCLC cohort.Methods: This study included patients with pathologically confirmed NSCLC, who were routinely screened for EGFR, KRAS, BRAF, ALK, ROS1, RET, MET, HER2, and PIK3CA mutations by the NMPA approved multi-gene detection kit. The demographic and clinicopathological data, treatment information, clinical outcomes after first-line treatment, as well as nine driver gene mutation statuses and PD-L1 expression level of these patients were retrospectively collected.Results: Finally, 431 patients were enrolled, most patients were male (55.9%), with adenocarcinoma or adenosquamous carcinoma (80.7%) and in stage IV (50.6%). Among all the 431 patients, 61.5% patients were identified with gene mutation including 101 with rare mutation, 164 with 19del or with L858R mutation. Adenocarcinoma patients have a higher mutation rate (73.6%), and the mutations mainly occur in EGFR, KRAS, ALK and HER2. While, the gene mutation characteristics in squamous cell carcinoma patients with were relatively simple, only 2 patients with EGFR 19del and 2 patients with PIK3CA mutation. More PD-L1 expression could detected in patients with rare mutation. The median PFS1 of patients with common mutation (13 months, 95% CI: 9.9-16) was longer than the patients with rare mutation (5 months, 95 % CI: 0-10.5). Conclusions: The clinicopathologic features and clinical treatment status among NSCLC patients with common or rare driver gene mutations were different. The survival of patients with rare mutation was worse than that of patients with common mutation. Therefore, more attention should be paid to the treatment strategy and survival status of patients with rare mutations in clinical practice.

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“…While ROS1 and ALK present high homology in their kinase domains, suggesting a similar effect on PD-L1 expression, there are current no preclinical data confirming this hypothesis. ROS1 positive tumors were poorly represented even in retrospective case series (27,47,48), preventing any conclusion about PD-L1 expression in this subgroup of patients. Importantly, ROS1 positive NSCLC shares with ALK-and RET-positive counterparts a lower TMB compared to wild type or EGFR-mutated adenocarcinomas (49).…”

Section: Pre-clinical Backgroundmentioning

confidence: 92%

Is there any place for immune-checkpoint inhibitors in the treatment algorithm of fusion-driven non-small cell lung cancer?—a literature review

Leone

Passiglia

Bironzo

et al. 2020

Transl Lung Cancer Res

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The advent of immune-checkpoint inhibitors (ICIs) targeting the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, produced a paradigm change of the treatment algorithm for metastatic, non-oncogene addicted, non-small cell lung cancer (NSCLC). However, the majority of patients with oncogene-addicted disease have been excluded from the "immunotherapy revolution", thus the clinical efficacy of these agents in this subset of patients remains largely unknown. Although pre-clinical evidence provided a good rationale to pursue the investigation of ICI treatment in specific subgroups of oncogeneaddicted NSCLC, current available evidence suggested that tumors harboring molecular alterations likely do not represent the best candidate to single agent ICI therapy. Furthermore, the prospect of further improving overall survival (OS) with the combination of tyrosine kinase inhibitors (TKIs) and ICIs led to unexpected poor results and safety issues in recent phase I trials exploring different therapeutic associations. Conversely, the combination of immunotherapy and chemotherapy is emerging as a potential effective strategy in specific subsets of NSCLC patients harboring oncogenic drivers. In this review we particularly focus on the subgroup of patients whose disease harbor oncogenic rearrangements, summarizing current evidence from preclinical and clinical studies and discussing their practical implications, in order to define the potential role of ICIs in the clinical management of fusion-driven NSCLC.

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Association between PD-L1 expression and driver gene mutations in non-small cell lung cancer patients: correlation with clinical data

Cited by 24 publications

References 50 publications

mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers

mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers

Pathological Signature and Therapeutic Status of NSCLC Patients with Common or Rare Driver Gene Alterations in North China：A real world retrospective study

Is there any place for immune-checkpoint inhibitors in the treatment algorithm of fusion-driven non-small cell lung cancer?—a literature review

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