Clinicopathological significance and prognostic value of E-cadherin expression in non-small cell lung cancer

et al. 2022

BMC Cancer

Background Recombinant human granulocyte colony-stimulating factor (rhG-CSF) reduces neutropenia events and is widely used in cancer patients receiving chemotherapy. However, the effects of rhG-CSF on distant organ metastasis (DOM) in non-small-cell lung cancer (NSCLC) patients following postoperative chemotherapy are not clear. Methods A retrospective cohort study was performed on NSCLC patients who underwent complete surgical resection and postoperative systemic chemotherapy at The First Affiliated Hospital of Nanchang University between 1 January 2012 and 31 December 2017. The effect of rhG-CSF on DOM was assessed with other confounding factors using Cox regression analyses. Results We identified 307 NSCLC patients who received postoperative systemic chemotherapy (n = 246 in the rhG-CSF group, n = 61 in the No rhG-CSF group). The incidence of DOM in postoperative NSCLC patients with rhG-CSF treatment was observably higher than in patients without rhG-CSF treatment (48.3% vs. 27.9%, p < 0.05). Univariate regression analysis revealed that rhG-CSF and pathological stage were independent risk factors for metastasis-free survival (MFS) (p < 0.05). RhG-CSF users had a higher risk of DOM (adjusted HR: 2.33, 95% CI: 1.31–4.15) than nonusers of rhG-CSF. The association between rhG-CSF and the risk of DOM was significant only in patients presenting with myelosuppression (HR: 3.34, 95% CI: 1.86–6.02) and not in patients without myelosuppression (HR: 0.71, 95% CI: 0.17–2.94, Interaction p-value< 0.01). The risk increased with higher dose density of rhG-CSF compared to rhG-CSF versus no users (p for trend< 0.001). Conclusion These analyses indicate that rhG-CSF use is related to DOM following postoperative chemotherapy in NSCLC.

Section: Resultssupporting

confidence: 91%

rhG-CSF is associated with an increased risk of metastasis in NSCLC patients following postoperative chemotherapy

Wang

et al. 2022

BMC Cancer

“…Sincerely, we found the different dosage and density gradients of rhG-CSF likely play an essential role in distant organ metastases (Table 2). Besides, clinical-stage were also associated with metastasis following NSCLC postoperative chemotherapy (Stage : HR 1.80, 95 % CI 1.02-3.19, p=0.04, Stage : HR 3.61, 95% CI 2.04-6.36, p<0.01), that is consistent with previous studies [12] .…”

Section: Prognostic Factors For Metastasissupporting

confidence: 91%

Recombinant Human Granulocyte Colony-Stimulating Factor is Associated with Increased Risk of Metastasis in NSCLC Patients Following Postoperative Chemotherapy: A Retrospective Cohort Study

Wang

Yuan

et al. 2021

Preprint

Background: Recombinant human granulocyte colony-stimulating factor (rhG-CSF), which can reduce neutropenia events, is widely used in cancer patients receiving chemotherapy. However, the effects of rhG-CSF on distant organ metastasis (DOM) in non-small cell lung cancer (NSCLC) patients following postoperative chemotherapy remain unclear.Methods: A retrospective cohort study was performed on NSCLC patients who suffered complete surgical resection and postoperative system chemotherapy at The First Affiliated Hospital of Nanchang University between 1 January 2012 and 31 December 2017. The effect of rhG-CSF on DOM was assessed, regulating with other confounding factors using Cox regression analyses.Results: We identified 307 NSCLC patients who received postoperative system chemotherapy (n=246 rhG-CSF group, n=61 No rhG-CSF group). The incidence of DOM in postoperative NSCLC patients with rhG-CSF treatment was observably higher than without rhG-CSF (48.3% vs. 27.9%, p<0.05). Univariate regression analysis revealed that rhG-CSF and clinical stage were the independent risk factor of Metastasis-free survival (MFS) (p<0.05). rhG-CSF users had a higher risk of DOM (adjusted HR: 2.33, 95% CI: 1.31-4.15) than nonusers of rhG-CSF. The association between rhG-CSF and risk of DOM was significant only among patients presenting with myelosuppression (HR: 3.34, 95% CI: 1.86-6.02), not among those without myelosuppression (HR: 0.71, 95% CI: 0.17-2.94, Interaction p-value<0.01). The risk increased with higher dosage density of rhG-CSF use, comparing those using rhG-CSF versus no users (p for trend<0.001).Conclusion These analyses indicated that rhG-CSF use is related to DOM following postoperative chemotherapy in NSCLC.

“…Fifteen pathways related to cell adhesion and immune and inflammatory responses were selected (Supplementary Table S2). Some cell adhesion molecules, which have been identified as tumor suppressor genes, are associated with a better prognosis in cancers (Sawada et al, 2020;Chao et al, 2021). Immune-and inflammation-related pathways such as "natural killer cell-mediated cytotoxicity," "B cell receptor signaling pathway," "cytokine-cytokine receptor interaction," "chemokine signaling pathway," "JAK-STAT signaling pathway," "T cell receptor signaling pathway" and "FC gamma R mediated phagocytosis," were also enriched in the LRMP high expression group.…”

Section: Discussionmentioning

confidence: 99%

LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma

Jin

Zhou

et al. 2021

Front. Mol. Biosci.

Background: Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear.Method: The expression levels of LRMP mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). LRMP protein expression was examined using the Human Protein Atlas. In vitro experiments, including qRT-PCR Western blot and immunohistochemistry staining were also performed to investigate LRMP expression. GEPIA2 and Kaplan-Meier plotter databases were used to analyze the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed using gene set enrichment analysis. Moreover, we also constructed plasmids to overexpress LRMP and explored the effect of LRMP in A549 cell line. Additionally, Tumor Immune single-cell Hub was used to investigate the distribution of LRMP in the LUAD immune microenvironment; TIMER and CIBERSORT were used to investigate the relationships among LRMP, LRMP co-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0.Results: The expression of LRMP was significantly lower in LUAD tissues and cell lines. High LRMP expression is associated with a better prognosis in patients with LUAD. In vitro experimental studies demonstrated that overexpression of LRMP could decrease the proliferation, migration and invasion in A549 cells, and downregulated multiple oncogenic signaling pathways, including p-STAT3, p-PI3K-p-AKT, p-MEK and EMT pathways. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. LRMP and its co-expressed genes were positively correlated with various tumor-infiltrating immune cells and their markers. Additionally, LRMP positively correlated with immune checkpoints.Conclusions: Our data suggest that LRMP may act as a tumor suppressor gene and indicates a better prognosis. Moreover, LRMP is associated with immune infiltrates which may be involved in immunotherapy response in LUAD. Further studies are needed to validate these findings.