Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer

Цыганов, М. М.; Родионов, Е. О.; Ибрагимова, М. К.; Миллер, С. В.; Черемисина, О. В.; Фролова, И Г; Тузиков, С. А.; Litviakov, N. V.

doi:10.3390/jpm12101647

Cited by 6 publications

(4 citation statements)

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“…Zhang et al demonstrated that significant correlation was observed in TYMS expression and clinical features, especially histology in NSCLC [ 51 ]. Tsyganov et al demonstrated that exploring TYMS expression could contribute to the personalized chemotherapy, which can improve treatment efficacy and reduce unnecessary toxicity [ 52 ]. In the present study, A549 and H1299 cells were transfected with siCDC6, siCEP55, and siTYMS, respectively.…”

Section: Discussionmentioning

confidence: 99%

Identifying lncRNAs and mRNAs related to survival of NSCLC based on bioinformatic analysis and machine learning

Yue,

Wang,

Lin

et al. 2024

Aging

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Non-small cell lung cancer (NSCLC) is the most common histopathological type, and it is purposeful for screening potential prognostic biomarkers for NSCLC. This study aims to identify the lncRNAs and mRNAs related to survival of non-small cell lung cancer (NSCLC). The expression profile data of lung adenocarcinoma and lung squamous cell carcinoma were downloaded in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. A total of eight survival related long non-coding RNAs (lncRNAs) and 262 survival related mRNAs were filtered. By gene set enrichment analysis, 17 significantly correlated Gene Ontology signal pathways and 14 Kyoto Encyclopedia of Genes and Genomes signal pathways were screened. Based on the clinical survival and prognosis information of the samples, we screened eight lncRNAs and 193 mRNAs by single factor Cox regression analysis. Further single and multifactor Cox regression analysis were performed, 30 independent prognostication-related mRNAs were obtained. The PPI network was further constructed. We then performed the machine learning algorithms (Least absolute shrinkage and selection operator, Recursive feature elimination, and Random forest) to screen the optimized DEGs combination, and a total of 17 overlapping mRNAs were obtained. Based on the 17 characteristic mRNAs obtained, we firstly built a Nomogram prediction model, and the ROC values of training set and testing set were 0.835 and 0.767, respectively. By overlapping the 17 characteristic mRNAs and PPI network hub genes, three genes were obtained: CDC6, CEP55, TYMS, which were considered as key factors associated with survival of NSCLC. The in vitro experiments were performed to examine the effect of CDC6, CEP55, and TYMS on NSCLC cells. Finally, the lncRNAs-mRNAs networks were constructed.

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Section: Discussionmentioning

confidence: 99%

Identifying lncRNAs and mRNAs related to survival of NSCLC based on bioinformatic analysis and machine learning

Yue,

Wang,

Lin

et al. 2024

Aging

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“…Наши предыдущие проспективные исследования рака молочной железы и легкого показали возможность применения оценки экспрессии генов ABC-транспортеров и генов химиочувствительности для персонализированного назначения схемы химиотерапии [33][34][35]. Согласно полученным данным снижение экспрессии ABC-генов в процессе лечения сопряжено с эффективностью химиотерапии и достижением более высоких показателей безметастатической выживаемости.…”

Section: успехи молекулярной онкологии / Advancesunclassified

Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases

et al. 2022

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Introduction. Metastatic tumors (particularly gastric cancer) have been found to be characterized by heterogeneity between the primary tumor and metastases. This type of heterogeneity comes to the fore when treating primary-metastatic forms of tumor and is an important reason for the low effectiveness of their treatment. In this regard, comparative analysis of ABC-transporter gene expression and chemosensitivity genes will allow to characterize to a certain extent the resistance and sensitivity of primary tumor, carcinomatosis and metastases to therapy and provide the basis for personalized treatment approach.Aim. To evaluate expression heterogeneity of ABC-transporter genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases.Materials and methods. Overall 41 patients with disseminated gastric cancer stage IV with carcinomatosis of peritoneum were included in the investigation. All patients underwent surgery according to Roux palliative gastrectomy. After surgery patients underwent chemotherapy depending on indications. RNA was isolated using RNeasy Plus mini kit (Qiagen, Germany). The expression level of ABC transporter genes (ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2) and chemosensitivity genes (BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, GSTP1) was assessed by reverse transcription polymerase chain reaction (RT-PCR) in primary tumor, carcinomatosis and lymph node metastases.Results. The expression levels of the genes under study were shown to vary widely. For ABC transporter genes, ABCG1 (3.1 ± 1.1; max 32.0), ABCG2 (7.9 ± 2.3; max 54.1), ABCG2 (9.6 ± 3.8; max 101.0) were the most expressed genes in gastric tumor tissue, carcinomatosis and lymph node metastasis, respectively. Hyperexpression among chemosensitivity genes at all three sites was characteristic only of TOP2α (17.2 ± 6.0; max. 161.9; 10.8 ± 4.1; max. 105.1; 35.3 ± 0.8; max. 439.6, respectively). We found that TOP2α and BRCA1 gene expression levels were higher in lymph node metastasis compared with gastric tumor tissue and carcinomatosis (at p = 0.005 and p = 0.001). Whereas ABCC1 gene expression was statistically significantly higher in carcinomatosis (p = 0.03).Conclusion. Thus, a high level of expression heterogeneity is observed in gastric cancer, which affects the expression patterns of various genes in different localizations. The expression profile can be used to determine the level of heterogeneity and approach to personalized therapy tactics.

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“…Однако доля пациентов, которым показаны эти методы лечения, не превышает 25 %, и даже у больных с показаниями для иммунотерапии ее эффективность составляет не более 15 %, поэтому основным методом лечения остается системная химиотерапия (ХТ), которая назначается эмпирически, без учета молекулярных мишеней ее действия. Высокая эффективность персонализированного назначения ХТ на основе оценки чувствительности и резистентности опухоли к определенным химиопрепаратам по экспрессии генов химиочувствительности показана в исследованиях, проведенных в нашем институте при немелкоклеточном раке легкого и раке молочной железы [18][19][20][21][22]. В то же время в литературе отсутствует информация о молекулярно-генетических исследованиях для выбора цитостатиков при раке желудка, в том числе и IV стадии.…”

Section: Introductionunclassified

Combined modality treatment of patients with stage IV gastric cancer with peritoneal carcinomatosis

et al. 2023

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Peritoneal carcinomatosis is associated with poor prognosis in gastric cancer patients. Stage IV gastric cancer (GC) is diagnosed in 39.8 % of patients; local metastases without evidence of distant metastases occur only in 18–20 % of stage IV gastric cancer patients.The purpose of the study was to estimate the efficacy of personalized chemotherapy in the combined modality treatment of patients with stage IV GC with peritoneal carcinomatosis.Material and Methods. Cytoreductive surgery was performed in 70 patients with GC with peritoneal dissemination. The control group patients (n=35) received postoperative chemotherapy with the FOLFOX regimen. The study group patients (n=35) received personalized systemic and intraperitoneal chemotherapy based on the expression of chemosensitivity and resistance genes.Results. The median survival time (18.7 months) in the study group patients was higher than that in the control group and in studies described in the world literature (CRS + HIPEC). Personalized chemotherapy improved median progressionfree survival (PFS) by 4.6 months (29.1 %) and median overall survival (OS) by 6 months (32 %) compared to FOLFOX regimen chemotherapy. In the study group, the 1-, 2and 3-year survival rates were observed in 35 (100 %), 9 (27 %) and 1 (3 %) patients, respectively.Conclusion. Personalized chemotherapy in the combined modality treatment can improve long-term treatment outcomes (longer median PFS and OS) in GC patients with peritoneal dissemination.

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Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer

Cited by 6 publications

References 37 publications

Identifying lncRNAs and mRNAs related to survival of NSCLC based on bioinformatic analysis and machine learning

Identifying lncRNAs and mRNAs related to survival of NSCLC based on bioinformatic analysis and machine learning

Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases

Combined modality treatment of patients with stage IV gastric cancer with peritoneal carcinomatosis

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