Common and differential features of liver and pancreatic cancers: molecular mechanism approach
Gastroenterology and Hepatology from Bed to Bench,
Vol. 14 No. Supplement 1 (2021),
30 December 2021
https://doi.org/10.22037/ghfbb.vi.2437
Abstract
Aim: The aim of this study was to introduce biomarkers commonly involved in pancreatic cancer metastasis to the liver.
Background: The liver is affected by metastatic disease in pancreatic cancer.
Methods: Two cancer biomarkers were distinguished through a STRING database protein query. The dysregulated proteins of the two cancers were included in 2 networks drawn by Cytoscape software v 3.2.7. 20 top nodes and achieved by the Network analyzer application of Cytoscape based on degree value. The common hub nodes were determined, and action maps were analyzed.
Results: Among 20 hubs of each studied cancer, 18 common hub nodes (90% of hubs) were identified and screened by action maps. Four proteins, AKT1, CDKN2A, ERBB2, and IL6, were identified as common central proteins related to the two studied diseases.
Conclusion: AKT1, CDKN2A, ERBB2, and IL6 are common protein core of liver and pancreatic cancers, while STAT3, CASP3, NOTCH1, and CTNNB1 are possible differential proteins to discriminate these cancers.
Keywords:
- Pancreas- ductal adenocarcinoma – liver cancer – Network analysis- Biomarker
How to Cite
Saki, K. ., Mansouri, V. ., Asri, N. . ., Fathi, M. ., & Razzaghi, Z. . (2021). Common and differential features of liver and pancreatic cancers: molecular mechanism approach. Gastroenterology and Hepatology from Bed to Bench, 14(Supplement 1). https://doi.org/10.22037/ghfbb.vi.2437
References
1. Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2016. CA: a cancer journal for clinicians, 2016. 66(1): p. 7-30.
2. Smeenk, H.G., et al., Adjuvant 5-FU-based chemoradiotherapy for patients undergoing R-1/R-2 resections for pancreatic cancer. Digestive surgery, 2005. 22(5): p. 321-328.
3. Dong, Y., et al., Liver-Metastasis-Related Genes are Potential Biomarkers for Predicting the Clinical Outcomes of Patients with Pancreatic Adenocarcinoma. Pathology and Oncology Research, 2021. 27.
4. Schnall, S.F. and J.S. Macdonald. Chemotherapy of adenocarcinoma of the pancreas. in Seminars in oncology. 1996.
5. Gleisner, A.L., et al., Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer: Interdisciplinary International Journal of the American Cancer Society, 2007. 110(11): p. 2484-2492.
6. Palmer, K., et al., Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Journal of British Surgery, 1994. 81(6): p. 882-885.
7. Glimelius, B., et al., Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Annals of oncology, 1996. 7(6): p. 593-600.
8. Shimizu, Y., et al., Small carcinoma of the pancreas is curable: new computed tomography finding, pathological study and postoperative results from a single institute. Journal of gastroenterology and hepatology, 2005. 20(10): p. 1591-1594.
9. Shi, H., J. Li, and D. Fu, Process of hepatic metastasis from pancreatic cancer: biology with clinical significance. Journal of cancer research and clinical oncology, 2016. 142(6): p. 1137-1161.
10. Bailey, P., et al., Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 2016. 531(7592): p. 47-52.
11. Buscail, L., B. Bournet, and P. Cordelier, Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nature Reviews Gastroenterology & Hepatology, 2020. 17(3): p. 153-168.
12. Jonckheere, N., et al., Unsupervised hierarchical clustering of pancreatic adenocarcinoma dataset from TCGA defines a mucin expression profile that impacts overall survival. Cancers, 2020. 12(11): p. 3309.
13. Li, Z., et al., Corrigendum: the OncoPPi network of cancer-focused protein–protein interactions to inform biological insights and therapeutic strategies. Nature communications, 2017. 8.
14. Makawita, S., et al., Integrated proteomic profiling of cell line conditioned media and pancreatic juice for the identification of pancreatic cancer biomarkers. Molecular & cellular proteomics, 2011. 10(10).
15. Ogura, T., et al., Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer. Journal of gastroenterology, 2013. 48(5): p. 640-646.
16. Cowgill, S.M. and P. Muscarella, The genetics of pancreatic cancer. The American journal of surgery, 2003. 186(3): p. 279-286.
17. Rezaei-Tavirani, M., et al., Pancreatic adenocarcinoma protein-protein interaction network analysis. Gastroenterology and Hepatology from bed to bench, 2017. 10(Suppl1): p. S85.
18. Qin, G., et al., Deciphering the protein–protein interaction network regulating hepatocellular carcinoma metastasis. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2017. 1865(9): p. 1114-1122.
19. Zhou, H., et al., Integrative microRNA-mRNA and protein-protein interaction analysis in pancreatic neuroendocrine tumors. Eur Rev Med Pharmacol Sci, 2016. 20(13): p. 2842-2852.
20. Seo, Y., et al., High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer, 2000. 88(10): p. 2239-2245.
21. Lu, Y., et al., Identification of Critical Pathways and Potential Key Genes in Poorly Differentiated Pancreatic Adenocarcinoma. OncoTargets and therapy, 2021. 14: p. 711.
22. McCaffery, I., et al., Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor. Clinical Cancer Research, 2013. 19(15): p. 4282-4289.
23. Szklarczyk, D., et al., The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic acids research, 2021. 49(D1): p. D605-D612.
24. Arjmand, B., et al., Assessment of molecular mechanism of saffron anti-stress property. Research Journal of Pharmacognosy, 2021. 8(3): p. 25-31.
25. Loftfield, E., et al., Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality. medRxiv, 2021.
26. Takesue, S., et al., Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts. International journal of oncology, 2020. 56(2): p. 596-605.
27. Costello, L.C., and Renty B Franklin. Pancreatic Cancer and Liver Cancer Are the Deadliest Cancers; and Still No Effective Chemo-therapy. Why. IJCMCR. 2021; 10 (3). 5.
28. Hsiue, E.H.-C., et al., Targeting a neoantigen derived from a common TP53 mutation. Science, 2021. 371(6533).
29. Datta, S.R., A. Brunet, and M.E. Greenberg, Cellular survival: a play in three Akts. Genes & development, 1999. 13(22): p. 2905-2927.
30. Sun, M., et al., AKT1/PKBα kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. The American journal of pathology, 2001. 159(2): p. 431-437.
31. West, K.A., S.S. Castillo, and P.A. Dennis, Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug resistance updates, 2002. 5(6): p. 234-248.
32. Vivanco, I. and C.L. Sawyers, The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nature Reviews Cancer, 2002. 2(7): p. 489-501.
33. Schlieman, M., et al., Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. British journal of cancer, 2003. 89(11): p. 2110-2115.
34. Yamamoto, S., et al., Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clinical Cancer Research, 2004. 10(8): p. 2846-2850.
35. Fahy, B.N., et al., Inhibition of AKT abrogates chemotherapy-induced NF-κB survival mechanisms: implications for therapy in pancreatic cancer. Journal of the American College of Surgeons, 2004. 198(4): p. 591-599.
36. Albury, T., et al., Constitutively Active Akt1 Cooperates with KRasG12D to Accelerate. 2015, vivo.
37. Zhen, D.B., et al., BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genetics in Medicine, 2015. 17(7): p. 569-577.
38. Goldstein, A.M., et al., Increased risk of pancreatic cancer in melanoma-prone kindreds with p16 INK4 mutations. New England Journal of Medicine, 1995. 333(15): p. 970-975.
39. McWilliams, R.R., et al., Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. European Journal of Human Genetics, 2011. 19(4): p. 472-478.
40. Serrano, M., G.J. Hannon, and D. Beach, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. nature, 1993. 366(6456): p. 704-707.
41. Biden, K., et al., Frequency of mutation and deletion of the tumor suppressor gene CDKN2A (MTS1/p16) in hepatocellular carcinoma from an Australian population. Hepatology, 1997. 25(3): p. 593-597.
42. Baek, M.J., et al., p16 is a major inactivation target in hepatocellular carcinoma. Cancer, 2000. 89(1): p. 60-68.
43. Matsuda, Y., et al., p16INK4 is inactivated by extensive CpG methylation in human hepatocellular carcinoma. Gastroenterology, 1999. 116(2): p. 394-400.
44. Kaneto, H., et al., Detection of hypermethylation of thep16INK4A gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus. Gut, 2001. 48(3): p. 372-377.
45. Shibata, W., et al., Overexpression of HER2 in the pancreas promotes development of intraductal papillary mucinous neoplasms in mice. Scientific reports, 2018. 8(1): p. 1-10.
46. Liu, J., et al., Increased expression of ErbB‐2 in liver is associated with hepatitis B× antigen and shorter survival in patients with liver cancer. International journal of cancer, 2009. 125(8): p. 1894-1901.
47. Razidlo, G.L., K.M. Burton, and M.A. McNiven, Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42. Journal of Biological Chemistry, 2018. 293(28): p. 11143-11153.
48. Thomas, H., IL-6 drives niche formation in pancreatic cancer liver metastasis. Nature Reviews Gastroenterology & Hepatology, 2019. 16(5): p. 263-263.
49. Scholz, A., et al., Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology, 2003. 125(3): p. 891-905.
50. Toyonaga, T., et al., Blockade of constitutively activated Janus kinase/signal transducer and activator of transcription-3 pathway inhibits growth of human pancreatic cancer. Cancer letters, 2003. 201(1): p. 107-116.
51. Zhong, Z., Z. Wen, and J.E. Darnell, Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science, 1994. 264(5155): p. 95-98.
52. Visconti, L., et al., Prognostic value of circulating cytokines on overall survival and disease-free survival in cancer patients. Biomarkers in medicine, 2014. 8(2): p. 297-306.
53. Crusz, S.M. and F.R. Balkwill, Inflammation and cancer: advances and new agents. Nature reviews Clinical oncology, 2015. 12(10): p. 584-596.
54. Persad, R., et al., Overexpression of caspase-3 in hepatocellular carcinomas. Modern Pathology, 2004. 17(7): p. 861-867.
55. Sun, B.-H., et al., Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21WAF1 expression and hepatic apoptosis. World journal of gastroenterology, 2000. 6(3): p. 356.
56. Miyamoto, Y., et al., Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer cell, 2003. 3(6): p. 565-576.
57. Hu, H., et al., Significance of NOTCH1 signaling pathway in human pancreatic development and carcinogenesis. Applied immunohistochemistry & molecular morphology: AIMM/official publication of the Society for Applied Immunohistochemistry, 2013. 21(3): p. 242.
58. Saukkonen, K., et al., PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma. BMC cancer, 2016. 16(1): p. 1-12.
59. Li, Y.-J., et al., β-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis. World journal of gastroenterology: WJG, 2005. 11(14): p. 2117.
60. Qiao, Q., et al., Reduced membranous and ectopic cytoplasmic expression of β‐catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer. International journal of cancer, 2001. 95(3): p. 194-197.
2. Smeenk, H.G., et al., Adjuvant 5-FU-based chemoradiotherapy for patients undergoing R-1/R-2 resections for pancreatic cancer. Digestive surgery, 2005. 22(5): p. 321-328.
3. Dong, Y., et al., Liver-Metastasis-Related Genes are Potential Biomarkers for Predicting the Clinical Outcomes of Patients with Pancreatic Adenocarcinoma. Pathology and Oncology Research, 2021. 27.
4. Schnall, S.F. and J.S. Macdonald. Chemotherapy of adenocarcinoma of the pancreas. in Seminars in oncology. 1996.
5. Gleisner, A.L., et al., Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer: Interdisciplinary International Journal of the American Cancer Society, 2007. 110(11): p. 2484-2492.
6. Palmer, K., et al., Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Journal of British Surgery, 1994. 81(6): p. 882-885.
7. Glimelius, B., et al., Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Annals of oncology, 1996. 7(6): p. 593-600.
8. Shimizu, Y., et al., Small carcinoma of the pancreas is curable: new computed tomography finding, pathological study and postoperative results from a single institute. Journal of gastroenterology and hepatology, 2005. 20(10): p. 1591-1594.
9. Shi, H., J. Li, and D. Fu, Process of hepatic metastasis from pancreatic cancer: biology with clinical significance. Journal of cancer research and clinical oncology, 2016. 142(6): p. 1137-1161.
10. Bailey, P., et al., Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 2016. 531(7592): p. 47-52.
11. Buscail, L., B. Bournet, and P. Cordelier, Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nature Reviews Gastroenterology & Hepatology, 2020. 17(3): p. 153-168.
12. Jonckheere, N., et al., Unsupervised hierarchical clustering of pancreatic adenocarcinoma dataset from TCGA defines a mucin expression profile that impacts overall survival. Cancers, 2020. 12(11): p. 3309.
13. Li, Z., et al., Corrigendum: the OncoPPi network of cancer-focused protein–protein interactions to inform biological insights and therapeutic strategies. Nature communications, 2017. 8.
14. Makawita, S., et al., Integrated proteomic profiling of cell line conditioned media and pancreatic juice for the identification of pancreatic cancer biomarkers. Molecular & cellular proteomics, 2011. 10(10).
15. Ogura, T., et al., Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer. Journal of gastroenterology, 2013. 48(5): p. 640-646.
16. Cowgill, S.M. and P. Muscarella, The genetics of pancreatic cancer. The American journal of surgery, 2003. 186(3): p. 279-286.
17. Rezaei-Tavirani, M., et al., Pancreatic adenocarcinoma protein-protein interaction network analysis. Gastroenterology and Hepatology from bed to bench, 2017. 10(Suppl1): p. S85.
18. Qin, G., et al., Deciphering the protein–protein interaction network regulating hepatocellular carcinoma metastasis. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2017. 1865(9): p. 1114-1122.
19. Zhou, H., et al., Integrative microRNA-mRNA and protein-protein interaction analysis in pancreatic neuroendocrine tumors. Eur Rev Med Pharmacol Sci, 2016. 20(13): p. 2842-2852.
20. Seo, Y., et al., High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer, 2000. 88(10): p. 2239-2245.
21. Lu, Y., et al., Identification of Critical Pathways and Potential Key Genes in Poorly Differentiated Pancreatic Adenocarcinoma. OncoTargets and therapy, 2021. 14: p. 711.
22. McCaffery, I., et al., Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor. Clinical Cancer Research, 2013. 19(15): p. 4282-4289.
23. Szklarczyk, D., et al., The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic acids research, 2021. 49(D1): p. D605-D612.
24. Arjmand, B., et al., Assessment of molecular mechanism of saffron anti-stress property. Research Journal of Pharmacognosy, 2021. 8(3): p. 25-31.
25. Loftfield, E., et al., Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality. medRxiv, 2021.
26. Takesue, S., et al., Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts. International journal of oncology, 2020. 56(2): p. 596-605.
27. Costello, L.C., and Renty B Franklin. Pancreatic Cancer and Liver Cancer Are the Deadliest Cancers; and Still No Effective Chemo-therapy. Why. IJCMCR. 2021; 10 (3). 5.
28. Hsiue, E.H.-C., et al., Targeting a neoantigen derived from a common TP53 mutation. Science, 2021. 371(6533).
29. Datta, S.R., A. Brunet, and M.E. Greenberg, Cellular survival: a play in three Akts. Genes & development, 1999. 13(22): p. 2905-2927.
30. Sun, M., et al., AKT1/PKBα kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. The American journal of pathology, 2001. 159(2): p. 431-437.
31. West, K.A., S.S. Castillo, and P.A. Dennis, Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug resistance updates, 2002. 5(6): p. 234-248.
32. Vivanco, I. and C.L. Sawyers, The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nature Reviews Cancer, 2002. 2(7): p. 489-501.
33. Schlieman, M., et al., Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. British journal of cancer, 2003. 89(11): p. 2110-2115.
34. Yamamoto, S., et al., Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clinical Cancer Research, 2004. 10(8): p. 2846-2850.
35. Fahy, B.N., et al., Inhibition of AKT abrogates chemotherapy-induced NF-κB survival mechanisms: implications for therapy in pancreatic cancer. Journal of the American College of Surgeons, 2004. 198(4): p. 591-599.
36. Albury, T., et al., Constitutively Active Akt1 Cooperates with KRasG12D to Accelerate. 2015, vivo.
37. Zhen, D.B., et al., BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genetics in Medicine, 2015. 17(7): p. 569-577.
38. Goldstein, A.M., et al., Increased risk of pancreatic cancer in melanoma-prone kindreds with p16 INK4 mutations. New England Journal of Medicine, 1995. 333(15): p. 970-975.
39. McWilliams, R.R., et al., Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. European Journal of Human Genetics, 2011. 19(4): p. 472-478.
40. Serrano, M., G.J. Hannon, and D. Beach, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. nature, 1993. 366(6456): p. 704-707.
41. Biden, K., et al., Frequency of mutation and deletion of the tumor suppressor gene CDKN2A (MTS1/p16) in hepatocellular carcinoma from an Australian population. Hepatology, 1997. 25(3): p. 593-597.
42. Baek, M.J., et al., p16 is a major inactivation target in hepatocellular carcinoma. Cancer, 2000. 89(1): p. 60-68.
43. Matsuda, Y., et al., p16INK4 is inactivated by extensive CpG methylation in human hepatocellular carcinoma. Gastroenterology, 1999. 116(2): p. 394-400.
44. Kaneto, H., et al., Detection of hypermethylation of thep16INK4A gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus. Gut, 2001. 48(3): p. 372-377.
45. Shibata, W., et al., Overexpression of HER2 in the pancreas promotes development of intraductal papillary mucinous neoplasms in mice. Scientific reports, 2018. 8(1): p. 1-10.
46. Liu, J., et al., Increased expression of ErbB‐2 in liver is associated with hepatitis B× antigen and shorter survival in patients with liver cancer. International journal of cancer, 2009. 125(8): p. 1894-1901.
47. Razidlo, G.L., K.M. Burton, and M.A. McNiven, Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42. Journal of Biological Chemistry, 2018. 293(28): p. 11143-11153.
48. Thomas, H., IL-6 drives niche formation in pancreatic cancer liver metastasis. Nature Reviews Gastroenterology & Hepatology, 2019. 16(5): p. 263-263.
49. Scholz, A., et al., Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology, 2003. 125(3): p. 891-905.
50. Toyonaga, T., et al., Blockade of constitutively activated Janus kinase/signal transducer and activator of transcription-3 pathway inhibits growth of human pancreatic cancer. Cancer letters, 2003. 201(1): p. 107-116.
51. Zhong, Z., Z. Wen, and J.E. Darnell, Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science, 1994. 264(5155): p. 95-98.
52. Visconti, L., et al., Prognostic value of circulating cytokines on overall survival and disease-free survival in cancer patients. Biomarkers in medicine, 2014. 8(2): p. 297-306.
53. Crusz, S.M. and F.R. Balkwill, Inflammation and cancer: advances and new agents. Nature reviews Clinical oncology, 2015. 12(10): p. 584-596.
54. Persad, R., et al., Overexpression of caspase-3 in hepatocellular carcinomas. Modern Pathology, 2004. 17(7): p. 861-867.
55. Sun, B.-H., et al., Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21WAF1 expression and hepatic apoptosis. World journal of gastroenterology, 2000. 6(3): p. 356.
56. Miyamoto, Y., et al., Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer cell, 2003. 3(6): p. 565-576.
57. Hu, H., et al., Significance of NOTCH1 signaling pathway in human pancreatic development and carcinogenesis. Applied immunohistochemistry & molecular morphology: AIMM/official publication of the Society for Applied Immunohistochemistry, 2013. 21(3): p. 242.
58. Saukkonen, K., et al., PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma. BMC cancer, 2016. 16(1): p. 1-12.
59. Li, Y.-J., et al., β-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis. World journal of gastroenterology: WJG, 2005. 11(14): p. 2117.
60. Qiao, Q., et al., Reduced membranous and ectopic cytoplasmic expression of β‐catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer. International journal of cancer, 2001. 95(3): p. 194-197.
- Abstract Viewed: 36 times
- pdf Downloaded: 32 times