Background: Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made it possible to identify genomic alterations that may influence response to lung cancer treatment. Methods: The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. Results:The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. HRAS mutations were present in most squamous cell carcinomas and adenocarcinomas of the lung. EcoR1-and Pst1-restriction enzymes destroyed the RT-PCR product of the p53 and p21Waf1 mRNA and increased the level of detected mutations in lung adenocarcinoma to 75% and 50 %, respectively. EGFR mutations were more frequent in lung adenocarcinoma than in lung squamous cell carcinoma. Mutations in EGFR exons 19 and 21 found in 65 of 263 lung tumor samples indicated the tumor sensitivity to EGFR tyrosine kinase inhibitors. EGFR deletions in exon 19 occurred mainly in adenocarcinoma, L858R mutations in EGFR exon 21 were quite common in lung adenocarcinoma. Conclusion: The mutations detected in most squamous cell carcinomas and adenocarcinomas of the lung could be used to diagnose and predict the disease severity and targeted therapy efficacy.
Relevance: According to the International Agency for Research on Cancer (IARС), breast cancer ranks 1st-2nd among other cancers globally [1], including Kazakhstan [2]. In Kazakhstan, the annual growth in breast cancer incidence exceeds 26.6%. In 2018-2019, breast cancer was the 3rd most common cause of cancer death in Kazakhstan, accounting for 8.7-8.1 percent, respectively. Early detection of breast cancer remains an acute issue. In particular, early detection should be improved. Epigenetic studies of cancer patients confirm that epigenetic biomarkers could be used as early cancer diagnostic markers, including breast cancer. The study aimed to find specific diagnostic markers by methylation profiling of peripheral blood mononuclear cell (PBMC) DNA in breast cancer patients. Results: Plasma samples of the Kazakhstani population with breast cancer possessed mononuclear cell methylation markers in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intergenic region on chromosome 5, chr5: 77,208,034-77,329,434, which were missing in healthy individuals. These biomarkers allow differentiating breast cancer from other cancers with a specificity of 0.91 and a sensitivity of 0.94 compared to methylation data from open DNA methylation databases (for Illumina 450K): TCGA, GSE40279, GSE61496, GSE76269 и GSE66836. Conclusion: Early breast cancer detection method using peripheral blood mononuclear cell DNA methylation profile, namely in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intergenic region on chromosome 5, chr5: 77,208,034-77,329,434 is enough specific and sensitive to use it in breast cancer screening.
Relevance: Along with other diagnostic methods, all current recommendations and protocols for malignant tumors’ diagnostics and treatment require mandatory molecular genetic testing at the initial diagnosis and in case of disease progression. The discovery of the BRAF gene mutation in skin melanoma allows the treatment with tyrosine kinase inhibitors, so-called BRAF inhibitors. This increases the probability of tumor response by half and opens up new therapeutic options. The study aimed to identify the BRAF V600E gene mutation frequency in patients with stage III-IV melanoma in the Republic of Kazakhstan to determine the need for targeted therapy. Results: 2251 persons are currently registered with melanoma in the Republic of Kazakhstan, with 355 new primary melanoma cases in 2019. Of them, 54% were diagnosed at stages III-IV and were subject to molecular genetic testing. 278 of 2251 patients were sent for BRAF mutations testing. The mutations were detected in 105 (37.7%) patients. Conclusion: The introduction of molecular genetic testing for malignant neoplasms under the Comprehensive Cancer Control Plan framework for 2018-2022 will increase the use of molecular genetic methods in the Republic of Kazakhstan. Molecular genetic testing is an important step in diagnosing melanoma and choosing the appropriate therapy to personalize cancer treatment.
IntroductionIncreased natural killer cells activity (NKCA) is linked to the reduced risk of colorectal cancer (CRC). Several prior studies investigated the association of NKCA and the incidence of CRC in high-risk subjects. The aim of our study was to investigate NKCA sensitivity in diagnosing advanced neoplasia and CRC in average risk population.Material and methodsNKCA was assessed by enzyme-linked immunosorbent assay (ELISA) blood test in average risk subjects with a range of 25-2500 pg/mL set for ELISA. NKCA higher than 200 pg/mL was defined as negative. The performance of NKCA was evaluated using the measures as sensitivity, specificity, negative and positive predictive values, clinical utility index, etc. In addition, odd ratios for developing CRC using logistic regression models were calculated.ResultsNKCA was evaluated in 354 average risk individuals (mean age 58.5 years-old; 36.2% males). The diagnostic accuracy of NKCA for CRC and AN has reached 75.5% and 72.3% respectively, with 96.4% NPV. NKCA test demonstrated good negative clinical utility index for CRC and AN (0.664 and 0.741, respectively). Individuals with low NKCA had 6.84 times higher odds to have CRC (95% CI 2.31-20.27; p<0.001). NKCA was higher in men vs. women (548.5 pg/mL vs. 500.0 pg/mL) and lower in smokers (412 pg/mL vs. 544 pg/mL), non-exercisers (413 pg/ml vs. 653.5 pg/mL), alcohol users (389 pg/mL vs. 476 pg/mL), and native Kazakhs and other Asian ethnic groups (446 pg/mL against 514 pg/mL).ConclusionsOur study suggests that high NKCA level has potential ability to rule out CRC and AN in average risk population.
Along with other diagnostic methods, all current recommendations and protocols for malignant tumors’ diagnostics and treatment require mandatory molecular genetic testing at the initial diagnosis and in case of disease progression. The discovery of the BRAF gene mutation in skin melanoma allows the treatment with tyrosine kinase inhibitors, so-called BRAF inhibitors. This increases the probability of tumor response by half and opens up new therapeutic options. The study aimed to identify the BRAF V600E gene mutation frequency in patients with stage III-IV melanoma in the Republic of Kazakhstan to determine the need for targeted therapy. Results: 2251 persons are currently registered with melanoma in the Republic of Kazakhstan, with 355 new primary melanoma cases in 2019. Of them, 54% were diagnosed at stages III-IV and were subject to molecular genetic testing. 278 of 2251 patients were sent for BRAF mutations testing. The mutations were detected in 105 (37.7%) patients. Conclusion: The introduction of molecular genetic testing for malignant neoplasms under the Comprehensive Cancer Control Plan framework for 2018-2022 will increase the use of molecular genetic methods in the Republic of Kazakhstan. Molecular genetic testing is an important step in diagnosing melanoma and choosing the appropriate therapy to personalize cancer treatment.
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