scholarly journals Expression of Microtubule-Associated Proteins in Relation to Prognosis and Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jieyan Luo ◽  
Qipeng Hu ◽  
Maling Gou ◽  
Xiaoke Liu ◽  
Yi Qin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Mrna Transcription ◽  
Small Cell Lung ◽  
Transcription Level ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
Nsclc Patients ◽  
The Relationship

BackgroundMicrotubule-associated proteins (MAPs) have been considered to play significant roles in the tumor evolution of non-small cell lung cancer (NSCLC). Nevertheless, mRNA transcription levels and prognostic value of distinct MAPs in patients with NSCLC remain to be clarified.MethodsIn this study, the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA) database, and Human Protein Atlas were utilized to analyze the relationship between mRNA/protein expression of different MAPs and clinical characteristics in NSCLC patients, including tumor type and pathological stage. The correlation between the transcription level of MAPs and overall survival (OS) of NSCLC patients was analyzed by Kaplan–Meier plotter. Besides, 50 frequently altered neighbor genes of the MAPs were screened out, and a network has been constructed via the cBioPortal and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) dataset. Meanwhile, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on the expression data of MAPs and their 50 frequently altered neighbor genes in NSCLC tissues. Furthermore, The Cancer Immunome Atlas (TCIA) was utilized to analyze the relationship between MAP expression and the response to immunotherapy. Finally, we used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to verify the expression of MAPs in 20 patients with NSCLC.ResultsThe present study discovered that the mRNA transcription levels of MAP7/7D2 were enriched in NSCLC tissues, while those of the MAP2/4/6/7D3 were lower in NSCLC specimens than those in control specimens. The mRNA transcription level of MAP6 was significantly associated with the advanced stage of NSCLC. Besides, survival analysis indicated that higher mRNA expressions of MAP2/4/6/7/7D3 were correlated considerably with favorable OS of NSCLC patients, whereas increased mRNA expression levels of MAP1A/1S were associated with poor OS. Moreover, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was significantly correlated with immunophenoscore (IPS) in NSCLC patients.ConclusionsOur analysis indicated that MAP1A/1S could serve as potential personalized therapeutic targets for patients with NSCLC, and the enriched MAP2/4/6/7/7D3 expression could serve as a biomarker for favorable prognosis in NSCLC. Besides, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was closely related to the response to immunotherapy. Taken together, MAP expression has potential application value in the clinical treatment and prognosis assessment of NSCLC patients, and further verifiable experiments can be conducted to verify our results.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

scholarly journals Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1794
Author(s):  
Alice Indini ◽  
Erika Rijavec ◽  
Francesco Grossi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Circulating Biomarkers ◽  
Small Cell Lung ◽  
Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

scholarly journals Feasibility and effectiveness of afatinib for poor performance status patients with EGFR-mutation-positive non-small-cell lung cancer: a retrospective cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chiao-En Wu ◽  
Ching-Fu Chang ◽  
Chen-Yang Huang ◽  
Cheng-Ta Yang ◽  
Chih-Hsi Scott Kuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Disease Control ◽  
Performance Status ◽  
Poor Performance ◽  
Small Cell ◽  
Poor Performance Status ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Afatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in patients with poor performance status (PS ≥ 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2. Methods The data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients’ clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy. Results Until February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control. Conclusion Afatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS.

scholarly journals 1318P Association between soluble PD-L1 and prognosis of non-small cell lung cancer (NSCLC) patients treated with immunotherapy

2020 ◽  
Vol 31 ◽  
pp. S851
Author(s):  
C. Dellepiane ◽  
S. Coco ◽  
M.G. Dal Bello ◽  
G. Rossi ◽  
E. Rijavec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luiz Henrique Araujo ◽  
Bianca Mendes Souza ◽  
Laura Rabelo Leite ◽  
Sabrina A. F. Parma ◽  
Natália P. Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Nsclc Patients

Abstract Background KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. Methods CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. Conclusions KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wang ◽  
Zhixuan Ren ◽  
Bentong Yu ◽  
Jian Tang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cancer Genomics ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Introduction Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC Methods In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics. Results 3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients. Conclusion Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.

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