Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin resistance remain elusive. In this study, we conducted an analysis of microarray data from the Gene Expression Omnibus (GEO) database under the accession numbers GSE21656, which encompassed expression profiling of cisplatin-resistant H460 (DDP-H460)and the parental cells (H460). Subsequently, we calculated the differentially expressed genes (DEGs) between DDP-H460 and H460. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs demonstrated significant impact on the Rap1, PI3K/AKT and MAPK signaling pathways. Moreover, protein and protein interaction (PPI) network analysis identified PRKCA, DET1, and UBE2N as hub genes that potentially contribute predominantly to cisplatin resistance. Ultimately, PRKCA was selected for validation due to its significant prognostic effect, which predicts unfavorable overall survival and disease-free survival in patients with lung cancer. Network analysis conducted on The Cancer Genome Atlas (TCGA) database revealed a strong gene-level correlation between PRKCA and TP53, CDKN2A, BYR2, TTN, KRAS, and PIK3CA; whereas at the protein level, it exhibited a high correlation with EGFR, Lck, Bcl2, and Syk. The in vitro experiments revealed that was upregulated in the cisplatin-resistant A549 cells (DDP-A549), while knockdown of PRKCA increased DDP-A549 apoptosis upon cisplatin treatment. Moreover, we observed that PRKCA knockdown attenuated DDP-A549 proliferation, migration and invasion ability. Western blot analysis demonstrated that PRKCA knockdown downregulated phosphorylation of PI3K expression while upregulated the genes involved in ferroptosis signaling. In summary, our results elucidate the role of PRKCA in acquiring resistance to cisplatin and underscore its potential as a therapeutic target for cisplatin-resistant lung cancer.
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http://dx.doi.org/10.1016/j.heliyon.2024.e30780 | DOI Listing |
Curr Pharm Des
January 2025
Department of Pharmacy, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.
Background: The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety.
View Article and Find Full Text PDFMed Chem
January 2025
Integrated Genetics and Molecular Oncology Group, Department of Genetic Engineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamilnadu, 603203, India.
Introduction: The marine habitat is a plentiful source of diverse, active compounds that are extensively utilised for their medicinal properties. Pharmaceutical trends have currently changed towards utilising a diverse range of goods derived from the marine environment.
Method: This study aimed to examine the inhibitory effects of bioactive chemicals derived from marine algae and bacteria.
Anticancer Agents Med Chem
January 2025
Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China.
Introduction: Immunotherapy targeting PD-1/PD-L1 shows significant benefits in lung cancer. Cutaneous immune-related adverse events (irAEs) are frequent, early-developing side effects of ICIs, and their potential role as prognostic markers in non-small cell lung cancer (NSCLC) therapy requires further exploration.
Methods: Data of patients with NSCLC treated with camrelizumab Combined with chemotherapy were collected at Xuzhou Medical University from 2019 to 2023.
Cancer Manag Res
January 2025
Department of Clinical Laboratory, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.
Purpose: (Tumor-educated platelets) TEPs have emerged as active players in all steps of tumorigenesis, confrontation of platelets with tumor cells via transfer of tumor-associated biomolecules and results in the sequestration of such biomolecules. The current study was aimed to examine whether TEPs lncRNA-STARD4-AS1 and ELOA-AS1 might be potential biomarkers for NSCLC.
Materials And Methods: TEPs were obtained by low-speed centrifugation.
Int J Med Sci
January 2025
Department of Laboratory Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
While NUSAP1's association with various tumors is established, its predictive value for prognosis and immunotherapy in lung adenocarcinoma (LUAD) remains unconfirmed. We analyzed Nucleolar Spindle-Associated Protein 1 (NUSAP1) gene expression in TCGA and GTEx datasets and validated it in clinicopathological tissues using qRT-PCR and immunohistochemistry. Additionally, we investigated NUSAP1's relationship with patient prognosis across TCGA and five GEO cohorts.
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