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Метаанализ исследований, посвященных прогностической значимости циркулирующей опухолевой ДНК при раке поджелудочной железы
Метаанализ исследований, посвященных прогностической значимости циркулирующей опухолевой ДНК при раке поджелудочной железы
Попова А.C., Федянин М.Ю., Покатаев И.А., Тюляндин С.А. Метаанализ исследований, посвященных прогностической значимости циркулирующей опухолевой ДНК при раке поджелудочной железы. Современная онкология. 2020; 22 (3): 127–132.
DOI: 10.26442/18151434.2020.3.200190
DOI: 10.26442/18151434.2020.3.200190
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Аннотация
Метод «жидкостной биопсии» позволяет определять циркулирующую опухолевую ДНК (цоДНК) в крови пациентов, однако клиническая значимость данного подхода при раке поджелудочной железы остается неясной. В связи с этим мы провели метаанализ работ, посвященных прогностической значимости цоДНК при раке поджелудочной железы.
Материалы и методы. Проведен поиск статей и абстрактов в базах данных PubMed, ASCO и ESMO, опубликованных до февраля 2020 г. и содержащих информацию о связи цоДНК и прогноза больных раком поджелудочной железы. К критериям исключения относили работы с 10 и менее участвующими в исследовании пациентами, отсутствием данных об относительном риске смерти и/или прогрессирования и 95% доверительном интервале к нему. Метаанализ проведен с помощью программы Review Manager (RevMan), version 5.3.
Результаты. Не отмечено существенных систематических ошибок, связанных с публикациями. Наличие цоДНК в крови пациентов негативно влияло на общую выживаемость пациентов (отношение риска – ОР 2,21, 95% доверительный интервал – ДИ 1,35–3,33, р=0,001) независимо от распространенности заболевания. В случае резектабельного процесса определение цоДНК в крови пациентов как до, так и после операции было фактором худшей выживаемости без признаков заболевания (ОР 2,32, 95% ДИ 1,54–3,5, р<0,0001 и ОР 3,06, 95% ДИ 1,63–5,76, р=0,0005 соответственно) и общей выживаемости (ОР 2,01, 95% ДИ 1,12–3,63, р=0,02 и ОР 3,39, 95% ДИ 2,12–5,44, р<0,00001 соответственно).
Выводы. Обнаружение цоДНК в крови больных раком поджелудочной железы является фактором негативного прогноза как при локализованном, так и при распространенном процессе. Необходимы дальнейшие проспективные исследования для выработки наиболее оптимального протокола определения цоДНК в крови пациентов.
Ключевые слова: рак поджелудочной железы, общая выживаемость, выживаемость без признаков заболевания, прогностический фактор, циркулирующая опухолевая ДНК.
Materials and methods. We carried out the search for the articles and abstracts in PubMed, ASCO and ESMO databases published before February 2020, containing data about the connection between ctDNA and the prognosis of pancreatic cancer. The exclusion criteria were the studies including 10 or less participating patients, absence of the data about the relative risk of mortality and/or progression, and the 95% confidence interval. The meta-analysis was carried out by using the Review Manager software (RevMan), Version 5.3.
Results. There were no significant systematic errors associated with the publications. The presence of ctDNA in patient blood showed poor overall survival of patients (odds ratio – OR 2.21, 95% confidence interval – CI 1.35-3.33, p=0.001) regardless of the prevalence of the disease. In case of the resectable process, the detection of ctDNA in patient blood both before and after surgery was a factor of worse progression-free survival (OR 2.32, 95% CI 1.54–3.5, p<0.001 and OR 3.06, 95% CI 1.63–5.76, р=0.0005 and overall survival (OR 2.01, 95% CI 1.12–3.63, р=0,02 and OR 3.39, 95% CI 2.12–5.44, р<0.00001, respectively).
Conclusions. The detection of ctDNA in the bloodstream in pancreatic cancer patients is a factor of poor prognosis in both localized and advanced cancer. It is very important to make further prospective studies to develop the optimal protocol for detecting ctDNA in patient bloodstream.
Key words: pancreatic cancer, the overall survival, disease-free survival, predictive factor, circulating tumor DNA.
Материалы и методы. Проведен поиск статей и абстрактов в базах данных PubMed, ASCO и ESMO, опубликованных до февраля 2020 г. и содержащих информацию о связи цоДНК и прогноза больных раком поджелудочной железы. К критериям исключения относили работы с 10 и менее участвующими в исследовании пациентами, отсутствием данных об относительном риске смерти и/или прогрессирования и 95% доверительном интервале к нему. Метаанализ проведен с помощью программы Review Manager (RevMan), version 5.3.
Результаты. Не отмечено существенных систематических ошибок, связанных с публикациями. Наличие цоДНК в крови пациентов негативно влияло на общую выживаемость пациентов (отношение риска – ОР 2,21, 95% доверительный интервал – ДИ 1,35–3,33, р=0,001) независимо от распространенности заболевания. В случае резектабельного процесса определение цоДНК в крови пациентов как до, так и после операции было фактором худшей выживаемости без признаков заболевания (ОР 2,32, 95% ДИ 1,54–3,5, р<0,0001 и ОР 3,06, 95% ДИ 1,63–5,76, р=0,0005 соответственно) и общей выживаемости (ОР 2,01, 95% ДИ 1,12–3,63, р=0,02 и ОР 3,39, 95% ДИ 2,12–5,44, р<0,00001 соответственно).
Выводы. Обнаружение цоДНК в крови больных раком поджелудочной железы является фактором негативного прогноза как при локализованном, так и при распространенном процессе. Необходимы дальнейшие проспективные исследования для выработки наиболее оптимального протокола определения цоДНК в крови пациентов.
Ключевые слова: рак поджелудочной железы, общая выживаемость, выживаемость без признаков заболевания, прогностический фактор, циркулирующая опухолевая ДНК.
________________________________________________
Materials and methods. We carried out the search for the articles and abstracts in PubMed, ASCO and ESMO databases published before February 2020, containing data about the connection between ctDNA and the prognosis of pancreatic cancer. The exclusion criteria were the studies including 10 or less participating patients, absence of the data about the relative risk of mortality and/or progression, and the 95% confidence interval. The meta-analysis was carried out by using the Review Manager software (RevMan), Version 5.3.
Results. There were no significant systematic errors associated with the publications. The presence of ctDNA in patient blood showed poor overall survival of patients (odds ratio – OR 2.21, 95% confidence interval – CI 1.35-3.33, p=0.001) regardless of the prevalence of the disease. In case of the resectable process, the detection of ctDNA in patient blood both before and after surgery was a factor of worse progression-free survival (OR 2.32, 95% CI 1.54–3.5, p<0.001 and OR 3.06, 95% CI 1.63–5.76, р=0.0005 and overall survival (OR 2.01, 95% CI 1.12–3.63, р=0,02 and OR 3.39, 95% CI 2.12–5.44, р<0.00001, respectively).
Conclusions. The detection of ctDNA in the bloodstream in pancreatic cancer patients is a factor of poor prognosis in both localized and advanced cancer. It is very important to make further prospective studies to develop the optimal protocol for detecting ctDNA in patient bloodstream.
Key words: pancreatic cancer, the overall survival, disease-free survival, predictive factor, circulating tumor DNA.
Полный текст
Список литературы
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12. Singh N, Gupta S, Pandey RM et al. High Levels of Cell-Free Circulating Nucleic Acids in Pancreatic Cancer are Associated With Vascular Encasement, Metastasis and Poor Survival. Cancer Investigation 2015; 33 (3): 78–85.
13. Hadano N, Murakami Y, Uemura K et al. Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. Br J Cancer 2016; 115 (1): 59–65.
14. Takai E, Totoki Y, Nakamura H et al. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. Sci Rep 2015; 5 (1): 18425.
15. Van Laethem JL, Riess H, Jassem J et al. Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. Targ Oncol 2017; 12 (1): 97–109.
16. Pietrasz D, Pécuchet N, Garlan F et al. Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker. Clin Cancer Res 2017; 23 (1): 116–23.
17. Adamo P, Cowley CM, Neal CP et al. Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer. Oncotarget 2017; 8 (50): 87221–33.
18. Lin M, Alnaggar M, Liang S et al. Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer. Cell Physiol Biochem 2018; 47 (4): 1556–64.
19. Nakano Y, Kitago M, Matsuda S et al. KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study. Br J Cancer 2018; 118 (5): 662–9.
20. Lee B, Lipton L, Cohen J et al. Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer. Ann Oncol 2019; 30 (9): 1472–8.
21. Patel H, Okamura R, Fanta P et al. Clinical correlates of blood-derived circulating tumor DNA in pancreatic cancer. J Hematol Oncol 2019; 12 (1): 130.
22. Seet AOL, Choo SP, Tai DW-M et al. Prognostic and predictive value of circulating tumour DNA (ctDNA) by amplicon-based next generation sequencing (NGS) of advanced pancreatic cancer (APC) in a phase I trial of oxaliplatin capecitabine and irinotecan (OXIRI) triplet chemotherapy. JCO 2020; 38 (4): 730.
23. Guo S, Shi X, Shen J et al. Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients. Br J Cancer 2020; 122: 857–67.
24. Meddeb R, Pisareva E, Thierry AR. Guidelines for the Preanalytical Conditions for Analyzing Circulating Cell-Free DNA. Clin Chemistry 2019; 65 (5): 623–33.
25. Gall TM, Frampton AE, Krell J et al. Circulating molecular markers in pancreatic cancer: ready for clinical use? Future Oncol 2013; 9 (2): 141–4.
26. Diehl F, Schmidt K, Choti MA et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14 (9): 985–90.
27. Chen L, Zhang Y, Cheng Y et al. Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis. Gene 2018; 679: 328–34.
28. Creemers A, Krausz S, Strijker M et al. Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis. Biochimica et Biophysica Acta (BBA). Rev Cancer 2017; 1868 (2): 394–403.
2. Sorenson GD, Pribish DM, Valone FH et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev 1994; 3 (1): 67–71.
3. Yamada T, Nakamori S, Ohzato H et al. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res 1998; 4 (6): 1527–32.
4. Cheng H, Liu C, Jiang J et al. Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients: Clinical value of ctDNA in metastatic pancreatic cancer. Int J Cancer 2017; 140 (10): 2344–50.
5. Del Re M, Vivaldi C, Rofi E et al. Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer. Sci Rep 2017; 7 (1): 7931.
6. Kim MK, Woo SM, Park B et al. Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma. Clin Chemistry 2018; 64 (4): 726–34.
7. Watanabe F, Suzuki K, Tamaki S et al. Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer. PLoS ONE 2019; 14 (12): e0227366.
8. Castells A, Puig P, Móra J et al. K-ras Mutations in DNA Extracted From the Plasma of Patients With Pancreatic Carcinoma: Diagnostic Utility and Prognostic Significance. JCO 1999; 17 (2): 578–84.
9. Chen H, Tu H, Meng ZQ, Chen Z et al. K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer. EJSO 2010; 36 (7): 657–62.
10. Earl J, Garcia-Nieto S, Martinez-Avila JC et al. Circulating tumor cells (CTC) and KRAS mutant circulating free DNA (cfDNA) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer. BMC Cancer 2015; 15 (1): 797.
11. Kinugasa H, Nouso K, Miyahara K et al. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer: K-ras in Blood With Pancreatic Cancer. Cancer 2015; 121 (13): 2271–80.
12. Singh N, Gupta S, Pandey RM et al. High Levels of Cell-Free Circulating Nucleic Acids in Pancreatic Cancer are Associated With Vascular Encasement, Metastasis and Poor Survival. Cancer Investigation 2015; 33 (3): 78–85.
13. Hadano N, Murakami Y, Uemura K et al. Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. Br J Cancer 2016; 115 (1): 59–65.
14. Takai E, Totoki Y, Nakamura H et al. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. Sci Rep 2015; 5 (1): 18425.
15. Van Laethem JL, Riess H, Jassem J et al. Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. Targ Oncol 2017; 12 (1): 97–109.
16. Pietrasz D, Pécuchet N, Garlan F et al. Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker. Clin Cancer Res 2017; 23 (1): 116–23.
17. Adamo P, Cowley CM, Neal CP et al. Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer. Oncotarget 2017; 8 (50): 87221–33.
18. Lin M, Alnaggar M, Liang S et al. Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer. Cell Physiol Biochem 2018; 47 (4): 1556–64.
19. Nakano Y, Kitago M, Matsuda S et al. KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study. Br J Cancer 2018; 118 (5): 662–9.
20. Lee B, Lipton L, Cohen J et al. Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer. Ann Oncol 2019; 30 (9): 1472–8.
21. Patel H, Okamura R, Fanta P et al. Clinical correlates of blood-derived circulating tumor DNA in pancreatic cancer. J Hematol Oncol 2019; 12 (1): 130.
22. Seet AOL, Choo SP, Tai DW-M et al. Prognostic and predictive value of circulating tumour DNA (ctDNA) by amplicon-based next generation sequencing (NGS) of advanced pancreatic cancer (APC) in a phase I trial of oxaliplatin capecitabine and irinotecan (OXIRI) triplet chemotherapy. JCO 2020; 38 (4): 730.
23. Guo S, Shi X, Shen J et al. Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients. Br J Cancer 2020; 122: 857–67.
24. Meddeb R, Pisareva E, Thierry AR. Guidelines for the Preanalytical Conditions for Analyzing Circulating Cell-Free DNA. Clin Chemistry 2019; 65 (5): 623–33.
25. Gall TM, Frampton AE, Krell J et al. Circulating molecular markers in pancreatic cancer: ready for clinical use? Future Oncol 2013; 9 (2): 141–4.
26. Diehl F, Schmidt K, Choti MA et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14 (9): 985–90.
27. Chen L, Zhang Y, Cheng Y et al. Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis. Gene 2018; 679: 328–34.
28. Creemers A, Krausz S, Strijker M et al. Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis. Biochimica et Biophysica Acta (BBA). Rev Cancer 2017; 1868 (2): 394–403.
2. Sorenson GD, Pribish DM, Valone FH et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev 1994; 3 (1): 67–71.
3. Yamada T, Nakamori S, Ohzato H et al. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res 1998; 4 (6): 1527–32.
4. Cheng H, Liu C, Jiang J et al. Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients: Clinical value of ctDNA in metastatic pancreatic cancer. Int J Cancer 2017; 140 (10): 2344–50.
5. Del Re M, Vivaldi C, Rofi E et al. Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer. Sci Rep 2017; 7 (1): 7931.
6. Kim MK, Woo SM, Park B et al. Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma. Clin Chemistry 2018; 64 (4): 726–34.
7. Watanabe F, Suzuki K, Tamaki S et al. Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer. PLoS ONE 2019; 14 (12): e0227366.
8. Castells A, Puig P, Móra J et al. K-ras Mutations in DNA Extracted From the Plasma of Patients With Pancreatic Carcinoma: Diagnostic Utility and Prognostic Significance. JCO 1999; 17 (2): 578–84.
9. Chen H, Tu H, Meng ZQ, Chen Z et al. K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer. EJSO 2010; 36 (7): 657–62.
10. Earl J, Garcia-Nieto S, Martinez-Avila JC et al. Circulating tumor cells (CTC) and KRAS mutant circulating free DNA (cfDNA) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer. BMC Cancer 2015; 15 (1): 797.
11. Kinugasa H, Nouso K, Miyahara K et al. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer: K-ras in Blood With Pancreatic Cancer. Cancer 2015; 121 (13): 2271–80.
12. Singh N, Gupta S, Pandey RM et al. High Levels of Cell-Free Circulating Nucleic Acids in Pancreatic Cancer are Associated With Vascular Encasement, Metastasis and Poor Survival. Cancer Investigation 2015; 33 (3): 78–85.
13. Hadano N, Murakami Y, Uemura K et al. Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. Br J Cancer 2016; 115 (1): 59–65.
14. Takai E, Totoki Y, Nakamura H et al. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. Sci Rep 2015; 5 (1): 18425.
15. Van Laethem JL, Riess H, Jassem J et al. Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. Targ Oncol 2017; 12 (1): 97–109.
16. Pietrasz D, Pécuchet N, Garlan F et al. Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker. Clin Cancer Res 2017; 23 (1): 116–23.
17. Adamo P, Cowley CM, Neal CP et al. Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer. Oncotarget 2017; 8 (50): 87221–33.
18. Lin M, Alnaggar M, Liang S et al. Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer. Cell Physiol Biochem 2018; 47 (4): 1556–64.
19. Nakano Y, Kitago M, Matsuda S et al. KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study. Br J Cancer 2018; 118 (5): 662–9.
20. Lee B, Lipton L, Cohen J et al. Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer. Ann Oncol 2019; 30 (9): 1472–8.
21. Patel H, Okamura R, Fanta P et al. Clinical correlates of blood-derived circulating tumor DNA in pancreatic cancer. J Hematol Oncol 2019; 12 (1): 130.
22. Seet AOL, Choo SP, Tai DW-M et al. Prognostic and predictive value of circulating tumour DNA (ctDNA) by amplicon-based next generation sequencing (NGS) of advanced pancreatic cancer (APC) in a phase I trial of oxaliplatin capecitabine and irinotecan (OXIRI) triplet chemotherapy. JCO 2020; 38 (4): 730.
23. Guo S, Shi X, Shen J et al. Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients. Br J Cancer 2020; 122: 857–67.
24. Meddeb R, Pisareva E, Thierry AR. Guidelines for the Preanalytical Conditions for Analyzing Circulating Cell-Free DNA. Clin Chemistry 2019; 65 (5): 623–33.
25. Gall TM, Frampton AE, Krell J et al. Circulating molecular markers in pancreatic cancer: ready for clinical use? Future Oncol 2013; 9 (2): 141–4.
26. Diehl F, Schmidt K, Choti MA et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14 (9): 985–90.
27. Chen L, Zhang Y, Cheng Y et al. Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis. Gene 2018; 679: 328–34.
28. Creemers A, Krausz S, Strijker M et al. Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis. Biochimica et Biophysica Acta (BBA). Rev Cancer 2017; 1868 (2): 394–403.
________________________________________________
2. Sorenson GD, Pribish DM, Valone FH et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev 1994; 3 (1): 67–71.
3. Yamada T, Nakamori S, Ohzato H et al. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res 1998; 4 (6): 1527–32.
4. Cheng H, Liu C, Jiang J et al. Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients: Clinical value of ctDNA in metastatic pancreatic cancer. Int J Cancer 2017; 140 (10): 2344–50.
5. Del Re M, Vivaldi C, Rofi E et al. Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer. Sci Rep 2017; 7 (1): 7931.
6. Kim MK, Woo SM, Park B et al. Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma. Clin Chemistry 2018; 64 (4): 726–34.
7. Watanabe F, Suzuki K, Tamaki S et al. Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer. PLoS ONE 2019; 14 (12): e0227366.
8. Castells A, Puig P, Móra J et al. K-ras Mutations in DNA Extracted From the Plasma of Patients With Pancreatic Carcinoma: Diagnostic Utility and Prognostic Significance. JCO 1999; 17 (2): 578–84.
9. Chen H, Tu H, Meng ZQ, Chen Z et al. K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer. EJSO 2010; 36 (7): 657–62.
10. Earl J, Garcia-Nieto S, Martinez-Avila JC et al. Circulating tumor cells (CTC) and KRAS mutant circulating free DNA (cfDNA) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer. BMC Cancer 2015; 15 (1): 797.
11. Kinugasa H, Nouso K, Miyahara K et al. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer: K-ras in Blood With Pancreatic Cancer. Cancer 2015; 121 (13): 2271–80.
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Авторы
А.C. Попова*1, М.Ю. Федянин1–3, И.А. Покатаев1,4, С.А. Тюляндин1
1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Российский университет дружбы народов», Москва, Россия;
3 ГБУЗ «Городская клиническая больница №40» Департамента здравоохранения г. Москвы, Москва, Россия;
4 ГБУЗ «Городская клиническая онкологическая больница №1» Департамента здравоохранения г. Москвы, Москва, Россия
*annpopova93@gmail.com
1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 People’s Friendship University of Russia, Moscow, Russia;
3 City Clinical Hospital №40, Moscow, Russia;
4 City Clinical Oncological Hospital №1, Moscow, Russia
*annpopova93@gmail.com
1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Российский университет дружбы народов», Москва, Россия;
3 ГБУЗ «Городская клиническая больница №40» Департамента здравоохранения г. Москвы, Москва, Россия;
4 ГБУЗ «Городская клиническая онкологическая больница №1» Департамента здравоохранения г. Москвы, Москва, Россия
*annpopova93@gmail.com
________________________________________________
1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 People’s Friendship University of Russia, Moscow, Russia;
3 City Clinical Hospital №40, Moscow, Russia;
4 City Clinical Oncological Hospital №1, Moscow, Russia
*annpopova93@gmail.com
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