Prognosis of Patients With Stages I and II Non-Small Cell Lung Cancer With Nodal Micrometastases

Gwozdz, Pawel; Pasieka-Lis, Monika; Kołodziej, Katarzyna; Pankowski, Juliusz; Banaś, Renata; Wilkojc, Michal; Zieliński, Marcin

doi:10.1016/j.athoracsur.2017.12.006

Cited by 21 publications

(14 citation statements)

References 17 publications

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“…Research by other authors also showed the feasibility of EBUS/TBNA samples of LNs for flow cytometric analysis of MTCs [42]. Moreover, a retrospective study performed by Gwozdz et al demonstrated that the presence of occult micrometastases in the mediastinal LNs was associated with reduced survival in I and II stage NSCLC patients due to tumor recurrence [43]. Their and our study demonstrated the usefulness of the EpCAM marker for the detection of early LNs cancer invasion.…”

Section: Discussionsupporting

confidence: 75%

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Raniszewska

Kwiecień

Sokołowski

et al. 2020

Cancers

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Over the past decade, immune checkpoint inhibitors have revolutionized the treatment of non-small cell lung cancer (NSCLC). Unfortunately, not all patients benefit from PD-(L)1 blockade, yet, the PD-L1 tumor cell expression is the only approved biomarker, and other biomarkers have been investigated. In the present study, we analyzed the presence of immunomodulatory molecules: PD-L1, CD47, CD73, Fas, and FasL on mature tumor cells (MTCs) and cancer stem cells (CSCs) in lymph nodes (LNs) aspirates and refer it to the lymphocyte subpopulation in peripheral blood (PB). PB samples and LNs aspirates obtained during the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS/TBNA) procedure of 20 patients at different stages of NSCLC. The cells were analyzed by multiparameter flow cytometry. We reported the higher frequency of MTCs and CSCs expressing the investigated immunomodulating molecules in metastatic LNs than in nonmetastatic. The expression of CD47 and PD-L1 was significantly higher on CSCs than on MTCs. Among the lymphocyte subpopulation in PB, we observed a higher frequency of PD-1+ CD8 T cells and Fas+ CD8 T cells in patients with confirmed metastases than in nonmetastatic. Next, we found that the percentage of FasL+ MTCs correlated with the frequency of Fas+ CD3 T cells in LNs aspirates and Fas+ CD8 T cells in PB. Finally, we found that patients with metastatic disease had a significantly higher FasL+/Fas+ MTCs ratio than patients with nonmetastatic disease. Both MTCs and CSCs express different immunomodulatory molecules on their surface. The frequency of FasL+ MTCs associates with altered distribution of Fas+ lymphocyte subpopulations in LNs and PB.

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Section: Discussionsupporting

confidence: 75%

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Raniszewska

Kwiecień

Sokołowski

et al. 2020

Cancers

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“…2 By the means of the TNM classification of malignant tumors, NSCLC is assigned with stage IA, IB, IIA, IIB, IIIA, IIIB, and IV based on the size of primary tumor, lymph node involvement, and distant metastasis. 3 Although the current therapeutical treatment for NSLCC including surgery, molecular-targeted therapy, and chemotherapy has been progressed tremendously in the last several decades, the prognosis is still poor with high metastasis of the NSLCC. 4,5 The 5-year survival of stage IV NSCLC patients is as low as 1%.…”

Section: Introductionmentioning

confidence: 99%

lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6

Liu

Chen

et al. 2019

J of Cellular Biochemistry

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Growing evidence have shown the important regulation of lncRNAs (long noncoding RNAs) in non–small cell lung cancer (NSCLC). lncRNA hepatocyte nuclear factor 1 homeobox A (HNF1A)‐antisense RNA 1 (AS1), an “oncogene”, was reported to regulate human tumors progression. However, the molecular mechanism of HNF1A‐AS1 involved in the development of NSCLC is still under investigation. In the current study, we found that HNF1A‐AS1 was relatively upregulated in both NSCLC patient tissues and cell lines. Functional studies established that overexpression of HNF1A‐AS1 promoted cell proliferation, cell cycle, invasion, and migration of NSCLC cells in vitro. The promotion abilities of HNF1A‐AS1 on NSCLC cell progression were suppressed via knockdown of HNF1A‐AS1. miR‐149‐5p was then proved to be a novel target of HNF1A‐AS1, whose expression was negatively correlated with HNF1A‐AS1 in NSCLC patient tissues and cell lines. HNF1A‐AS1 increased the expression of cyclin‐dependent kinase 6 (Cdk6) via sponging with miR‐149‐5p. Gain‐ and loss‐of‐functional studies indicated that HNF1A‐AS1 promoted NSCLC progression partially through inhibition of miR‐363‐3p and induction of Cdk6. Subcutaneous xenotransplanted tumor model confirmed that interference of HNF1A‐AS1 suppressed the tumorigenic ability of NSCLC via upregulation of miR‐149‐5p and downregulation of Cdk6 in vivo. In conclusion, our findings clarified the biologic significance of the HNF1A‐AS1/miR‐149‐5p/Cdk6 axis in NSCLC progression and provided novel evidence that HNF1A‐AS1 may be a new potential therapeutic target for the treatment of NSCLC.

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“…FNA is a low-invasive procedure, useful for the recognition of lung cancer metastases in many body organs such as mediastinal lymph nodes, superficial (e.g., supraclavicular) lymph nodes, the liver, adrenal lesions, metastases to soft tissue, etc. Gwozdz P et al recently discussed the progress in pathological diagnosis, pointing to the usefulness of IHC staining with pan-cytokeratine antibodies to detect occult micrometastases of significant value for cancer prognosis (30). Due to the simplicity of the method lung cancer is very often recognized not on the basis of primary tumor examination but from metastasis.…”

Section: Lung Cancer In Light Microscopymentioning

confidence: 99%

New Frontiers for Molecular Pathology

Domagała‐Kulawik

2019

Front. Med.

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Lung cancer remains a serious oncological problem worldwide. The delayed diagnosis and a prevalence of advanced stages in up to 70% of cases at recognition are still observed. Thanks to targeted therapies and immunotherapy a significant progress in achieving prolonged survival in some lung cancer patients is reported. A precise histopathological diagnosis, especially the recognition of adenocarcinoma, and a progress in the methods of clinical staging underlie the proper qualification of patients for a tailored therapy. The deep molecular characteristics of lung cancer in liquid biopsy, for example blood, bronchoalveolar lavage fluid (BALF), cell suspension from needle aspirates, are currently available. The molecular characteristic has recently been extended with molecular aberrations of BRAF, KRAS, MET, ERBB2, RET, NTRK next to the well-known EGFR mutations and ALK, ROS-1 relocation. The present paper discusses the usefulness of adequate pathological methods and molecular testing for the identification of a broad spectrum of predictive biomarkers for a molecular-directed lung cancer therapy. Immunotherapy with immune checkpoint inhibitors (ICIs) is approved in the first line therapy of advanced non-small-cell lung cancer. To date only PD-L1 expression on tumor cells has been found to be a marker of response to ICIs. The efficacy of ICIs as well as the susceptibility to immune-related adverse events are highly individual, so immune biomarkers are widely investigated. The candidates for predictive factors for ICIs immunotherapy include cancer cell antigenicity, presence of regulatory/suppressory molecules on cancer cells, cancer stem cells or on exosomes, and, on the other hand, an immune status of the patient. Cancers with high immune infiltration in the tumor milieu, referred to as “hot” tumors, seem to ensure a better response to ICIs than the “cold” ones. BALF analysis may replace cancer tissue examination, which is of limited access in advanced stages, for the recognition of the nature of immune response in the tumor environment. Tumor mutational burden (TMB) was shown to correlate with a good response to ICIs, especially when combined with other anticancer therapies. The present paper demonstrates the results of recent studies on lung cancer characteristics which bring us closer to the definition of useful prognostic/predictive factors.

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Prognosis of Patients With Stages I and II Non-Small Cell Lung Cancer With Nodal Micrometastases

Cited by 21 publications

References 17 publications

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6

New Frontiers for Molecular Pathology

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