Journal of Cancer
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Objective: The microsatellite status and tumor immune microenvironment have a remarkable influence on tumor immunotherapy. This study was performed to investigate programmed cell death protein 1/programmed death ligand 1 (PD1/PDL1) expression and their correlations with CD8+ T cell/CD68+ macrophage (CD68+ M) densities in gastric cancer (GC) at different microsatellite statuses. Methods: The expression of MLH1, PMS2, MSH2, and MSH6 was detected via immunohistochemistry (IHC) to determine the microsatellite status in 215 GC samples obtained from surgical resections. ⋯ Conclusion: The results suggested that PD1/PDL1 expression and immune response varied at different microsatellite statuses in GC. PD1/PDL1 expression was correlated with CD8+ T cell/CD68+ M densities in GC at different microsatellite statuses, especially at the invasion front. The patients exhibiting high PD1/PDL1 expression or high CD8+ T cell/CD68+ M densities MSI GC might be potential beneficiaries of PD1/PDL1 immunotherapy.
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Objectives: Cancer cells usually escape tumor-reactive T-cell responses using immune checkpoint proteins, such as programmed death protein-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1). These proteins can be blocked by immune checkpoint inhibitors (ICIs); the decision on ICI-based first-line treatment for advanced lung cancers depends on the PD-L1 levels in tumor specimens. Determining the PD-L1 expression conventionally requires histological specimens from resected tumors and core biopsy specimens. ⋯ Among the 19 SCLC patients, 16 (84.2%) exhibited no PD-L1 expression in both EBUS-TBNA and TBB specimens. Notably, the progression-free survival of patients with ≥50% PD-L1 expression in the paired specimens who received ICI treatment was 8.3 months. Conclusion: Collectively, our results validate the use of EBUS-TBNA specimens for the determination of the PD-L1 expression levels in the context of NSCLC and SCLC.
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We aimed to determine whether Neuropilin-1 (NRP1) promotes gastric cancer (GC) metastasis by inducing epithelial-mesenchymal transition (EMT), and to clarify its regulatory mechanism. Using the data of GC patients in The Cancer Genome Atlas (TCGA) and Gene Tissue Expression (GTEx) databases, combined with the data of GC patients in our medical center, the effect of NRP1 on the prognosis of GC patients were analyzed. Then, we investigated the role of NRP1 in GC metastasis and its potential mechanism. ⋯ This study determined that NRP1 was a gene that promotes gastric cancer. NRP1 induced EMT to enhance the migration and invasion ability of GC cells by activating PI3K/Akt signaling pathway. NRP1 was an independent prognostic marker for OS in GC patients and expected to be a therapeutic target for GC patients.
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Background: Ribonucleoside-diphosphate reductase subunit M2 (RRM2) is the catalytic subunit of ribonucleotide reductase and modulates the enzymatic activity, which is essential for DNA replication and repair. However, the role of RRM2 in lung adenocarcinoma (LUAD) remains unclear. Methods: In this study, we explored the expression pattern and prognostic value of RRM2 in LUAD across TCGA, GEO, Oncomine, UALCAN, PrognoScan, and Kaplan-Meier Plotter, and confirmed its independent prognostic value via Cox analyses. ⋯ Conclusion: Our research showed that RRM2 could independently predict the prognosis of LUAD and was associated with immune infiltration. In particular, the tight relationship between RRM2 and B cell marker genes are the potential epicenter of the immune response and one of the critical factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of RRM2 in LUAD.
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Melanoma is the most aggressive and treatment-resistant form of skin cancer. Curcumol is a Chinese medicinal herb traditionally used as a cancer remedy. However, the molecular mechanisms underlying the anticancer activity of curcumol in melanoma remains largely unknown. ⋯ Reduced expression of miR-152-3p partially attenuated the effect of curcumol on mouse melanoma B16 cell proliferation and migration. The decrease in c-MET, P13K and p-AKT protein expression following curcumol treatment in mouse melanoma B16 cells was notably attenuated by the miR-152-3p inhibitor. Taken together, our findings suggested that curcumol attenuated melanoma progression and concomitantly suppressed ERK/NF-κB signaling and promoted miR-152-3p expression to inactivate the c-MET/PI3K/AKT signaling pathway.