Association between the expression of CXCL12/CXCR4 and pancreatic cancer: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CAO Wei ¹ , CHENG Mengqiu ¹ ,  CHEN Bo ²

1. First School of Clinical Medicine, Anhui Medical University, Hefei 230000, P.R.China;
2. Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230000, P.R.China;

Corresponding?author：

CHEN Bo, Email: chenbo831116@163.com

Keywords：

Pancreatic cancer; Chemokine CXCL12; Chemokine receptor CXCR4; Meta-analysis; Systematic review; Case-control study

DOI：

10.7507/1672-2531.202002093

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the relationship between the expression of CXCL12/CXCR4 and pancreatic cancer.Methods PubMed, EMbase, The Cochrane Library, Wiley Online Library, CNKI, VIP, WanFang Data and CBM databases were electronically searched to collect case-control studies on CXCL12/CXCR4 expression in pancreatic cancer from inception to February 1^st 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 software.Results A total of 21 case-control studies involving 1 677 cases and 1 690 controls were included. The results of meta-analysis showed that the expression of CXCR4 in pancreatic cancer tissue was higher than normal tissue (OR=21.40, 95%CI 5.70 to 80.31, P<0.01), in carcinoma of head of pancreas been higher than carcinoma of pancreatic body and tail, (OR=1.58, 95%CI 1.02 to 2.44, P=0.04), in pancreatic cancer with lymph node metastasis been higher than without lymph node metastasis (OR=3.14, 95%CI 1.98 to 4.99, P<0.01), in pancreatic cancer with high TNM stages (Ⅲ, Ⅳ) been higher than low TNM stages (Ⅰ, Ⅱ) (OR=3.67, 95%CI 1.98 to 6.81, P<0.01), in pancreatic cancer with distant metastasis been higher than without distant metastasis (OR=3.56, 95%CI 1.71 to 7.39, P<0.01), and in pancreatic cancer with vascular invasion was higher than without vascular invasion (OR=3.22, 95%CI 1.70 to 6.09, P<0.01). The expression of CXCR4 was not statistically correlated with age, gender, pancreatic cancer tissue and paracancerous tissue, pancreatic cancer tissue and paracancerous lymph nodes, differentiation degree. There was no statistical correlation between the expression of CXCL12 and the differentiation degree, and lymph node metastasis.Conclusions In pancreatic cancer, the high expression of CXCR4 is related to lymph node metastasis, high TNM stage, distant metastasis, vascular invasion indicate poor prognosis. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.

Citation： CAO Wei, CHENG Mengqiu, CHEN Bo. Association between the expression of CXCL12/CXCR4 and pancreatic cancer: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2021, 21(2): 179-185. doi: 10.7507/1672-2531.202002093 Copy

1.	吳萬龍, 彭兵. 胰腺癌流行病學及危險因素. 中國普外基礎與臨床雜志, 2019, 26(12): 1500-1504.
2.	馬少軍, 屈振亮, 孔棣, 等. 胰腺癌流行病學及診斷研究進展. 中國中西醫結合外科雜志, 2015, 21(1): 87-92.
3.	呂翼, 魏若征, 吳河水. 胰腺癌的早期診斷. 臨床急診雜志, 2018, 19(3): 149-151.
4.	劉夢奇, 吉順榮, 徐曉武, 等. 2019年胰腺癌研究及診療新進展. 中國癌癥雜志, 2020, 30(1): 1-10.
5.	張師容, 靳偉, 劉亮, 等. 2017年胰腺癌基礎研究及診療新進展. 中國癌癥雜志, 2018, 28(1): 1-10.
6.	潘博, 郭俊超, 廖泉, 等. 吉西他濱與胰腺癌化療耐藥. 中國普外基礎與臨床雜志, 2005, (5): 530-532.
7.	陳菊香, 周紅軒, 馬蘭, 等. 吉西他濱聯合奧沙利鉑或替吉奧對比吉西他濱單藥治療晚期胰腺癌臨床觀察. 安徽醫藥, 2015, 19(2): 359-362.
8.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
9.	Righetti A, Giulietti M, Sabanovic B, et al. CXCL12 and its isoforms: different roles in pancreatic cancer? J Oncol, 2019, 2019 (8): 1-13.
10.	Lombardi L. Chemokine receptor CXCR4: What is its role in gastrointestinal cancer? J Clin Oncol, 2013, 31(15).
11.	Nazari A, Khorramdelazad H, Hassanshahi G. Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer. Int J Clin Oncol, 2017, 22(6): 991-1000.
12.	Kajtazi Y, Kaemmerer D, S?nger J, et al. Somatostatin and chemokine CXCR4 receptor expression in pancreatic adenocarcinoma relative to pancreatic neuroendocrine tumours. J Cancer Res Clin Oncol, 2019, 145(10): 2481-2493.
13.	Zhou W, Guo S, Liu M, et al. Targeting CXCL12/CXCR4 axis in tumor immunotherapy. Curr Med Chem, 2019, 26(17): 3026-3041.
14.	Morimoto M, Matsuo Y, Koide S, et al. Enhancement of the CXCL12/CXCR4 axis due to acquisition of gemcitabine resistance in pancreatic cancer: effect of CXCR4 antagonists. BMC Cancer, 2016, 16(305).
15.	張紅雨, 費立明, 王長亮, 等. 胰腺癌中CXCL12-CXCR4生物學軸與VEGF-C的表達及相關性研究. 中國現代普通外科進展, 2008, 11(4): 283-286.
16.	喻建, 曹軍. VEGF-C, CXCR4在胰腺癌中的表達與意義. 醫學新知雜志, 2008, 18(6): 342-343, 345.
17.	姚寶忠, 李良, 江鳴, 等. CD133和趨化因子受體4在胰腺癌中的表達及臨床相關性. 中華普通外科學文獻(電子版), 2017, 11(6): 375-379.
18.	許瑩, 潘振國, 李倩君, 等. GSK3β, CXCR4, MMP-2與胰腺癌侵襲和轉移的關系. 胃腸病學和肝病學雜志, 2016, 25(11): 1308-1311.
19.	徐鋒. SDF-1/CXCR4和TECK/CCR9與胰腺癌預后不良相關性研究. 天津: 天津醫科大學, 2013.
20.	王寶勝, 孟祥鵬, 劉臻, 等. 胰腺癌組織中SDF-1的表達與其臨床病理特征的關系. 現代腫瘤醫學, 2012, 20(3): 540-542.
21.	李玉軍, 李霞, 孫玲玲, 等. 胰腺癌CXCR-4, MMP-2, VEGF的表達及其與腫瘤生物學行為的關系. 中華胰腺病雜志, 2009, 9(5): 334-336.
22.	李輝, 呂麗紅, 張波, 等. CXCR-4在胰腺癌中的表達及臨床意義. 山東醫藥, 2008, 48(6): 64-65.
23.	符亮, 吳冬冰, 萬鴻興. 胰腺癌組織轉錄中介因子1及趨化因子受體-4的表達特點及臨床意義. 安徽醫藥, 2019, 23(9): 1842-1845.
24.	方德剛, 周光華. 人胰腺癌變組織中血管內皮生長因子微血管密度CXCR-4的表達及其意義. 山西醫藥雜志, 2011, 40(12): 1180-1181.
25.	Zhang J, Liu C, Mo X, et al. Mechanisms by which CXCR4/CXCL12 cause metastatic behavior in pancreatic cancer. Oncol Lett, 2018, 15(2): 1771-1776.
26.	Xu Q, Wang Z, Chen X, et al. Stromal-derived factor-1α/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer. Oncotarget, 2015, 6(7): 4717-4732.
27.	Wehler T, Wolfert F, Schimanski CC, et al. Strong expression of chemokine receptor CXCR4 by pancreatic cancer correlates with advanced disease. Oncol Rep, 2006, 16(6): 1159-1164.
28.	Wang Z, Ma Q, Li P, et al. Aberrant expression of CXCR4 and β-catenin in pancreatic cancer. Anticancer Res, 2013, 33(9): 4103-4110.
29.	Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. Clin Cancer Res, 2000, 6(9): 3530-3535.
30.	Liang JJ, Zhu S, Bruggeman R, et al. High levels of expression of human stromal cell-derived factor-1 are associated with worse prognosis in patients with stage Ⅱ pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev, 2010, 19(10): 2598-2604.
31.	Jiang YM, Li G, Sun BC, et al. Study on the relationship between CXCR4 expression and perineural invasion in pancreatic cancer. Asian Pac J Cancer Prev, 2014, 15(12): 4893-4896.
32.	Wu H, Zhu L, Zhang H, et al. Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma. PLoS One, 2015, 10(2): e116803.
33.	Liao W, Wang H, Huang H, et al. CXCR4 expression predicts early liver recurrence and poor survival after resection of pancreatic adenocarcinoma. Clin Transl Gastroenterol, 2012, 3(9): e22.
34.	Marechal R, Demetter P, Nagy N, et al. High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma. Br J Cancer, 2009, 100(9): 1444-1451.
35.	Gebauer F, Tachezy M, Effenberger K, et al. Prognostic impact of CXCR4 and CXCR7 expression in pancreatic adenocarcinoma. J Surg Oncol, 2011, 104(2): 140-145.
36.	彭松慶. 血清基質金屬蛋白酶9和CC型趨化因子18對胰腺癌診斷性能評價. 中國衛生檢驗雜志, 2017, 27(23): 3417-3418.
37.	郭欣, 呂行, 謝嬌貴, 等. 趨化因子配體18表達水平對胰腺癌患者的預后價值. 中華肝膽外科雜志, 2015, 21(7): 474-477.
38.	孫聯康, 都大偉, 錢偉崐, 等. 趨化因子CXCL11激活NF-κB信號通路促進胰腺癌的侵襲轉移及上皮間質轉換. 西安交通大學學報(醫學版), 2019, 40(4): 501-505.
39.	Zhang R, Liu Q, Peng J, et al. CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration. J Cancer, 2020, 11(9): 2371-2381.
40.	Fan H, Wang W, Yan J, et al. Prognostic significance of CXCR7 in cancer patients: a meta-analysis. Cancer Cell Int, 2018, 18: 212.
41.	Litman-Zawadzka A, ?ukaszewicz-Zaj?c M, Gryko M, et al. Serum chemokine CXCL8 as a better biomarker for diagnosis and prediction of pancreatic cancer than its specific receptor CXCR2, c-reactive protein, and classic tumor markers CA 19-9 and CEA. Pol Arch Intern Med, 2018, 128(9): 524-531.

1. 吳萬龍, 彭兵. 胰腺癌流行病學及危險因素. 中國普外基礎與臨床雜志, 2019, 26(12): 1500-1504.
2. 馬少軍, 屈振亮, 孔棣, 等. 胰腺癌流行病學及診斷研究進展. 中國中西醫結合外科雜志, 2015, 21(1): 87-92.
3. 呂翼, 魏若征, 吳河水. 胰腺癌的早期診斷. 臨床急診雜志, 2018, 19(3): 149-151.
4. 劉夢奇, 吉順榮, 徐曉武, 等. 2019年胰腺癌研究及診療新進展. 中國癌癥雜志, 2020, 30(1): 1-10.
5. 張師容, 靳偉, 劉亮, 等. 2017年胰腺癌基礎研究及診療新進展. 中國癌癥雜志, 2018, 28(1): 1-10.
6. 潘博, 郭俊超, 廖泉, 等. 吉西他濱與胰腺癌化療耐藥. 中國普外基礎與臨床雜志, 2005, (5): 530-532.
7. 陳菊香, 周紅軒, 馬蘭, 等. 吉西他濱聯合奧沙利鉑或替吉奧對比吉西他濱單藥治療晚期胰腺癌臨床觀察. 安徽醫藥, 2015, 19(2): 359-362.
8. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
9. Righetti A, Giulietti M, Sabanovic B, et al. CXCL12 and its isoforms: different roles in pancreatic cancer? J Oncol, 2019, 2019 (8): 1-13.
10. Lombardi L. Chemokine receptor CXCR4: What is its role in gastrointestinal cancer? J Clin Oncol, 2013, 31(15).
11. Nazari A, Khorramdelazad H, Hassanshahi G. Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer. Int J Clin Oncol, 2017, 22(6): 991-1000.
12. Kajtazi Y, Kaemmerer D, S?nger J, et al. Somatostatin and chemokine CXCR4 receptor expression in pancreatic adenocarcinoma relative to pancreatic neuroendocrine tumours. J Cancer Res Clin Oncol, 2019, 145(10): 2481-2493.
13. Zhou W, Guo S, Liu M, et al. Targeting CXCL12/CXCR4 axis in tumor immunotherapy. Curr Med Chem, 2019, 26(17): 3026-3041.
14. Morimoto M, Matsuo Y, Koide S, et al. Enhancement of the CXCL12/CXCR4 axis due to acquisition of gemcitabine resistance in pancreatic cancer: effect of CXCR4 antagonists. BMC Cancer, 2016, 16(305).
15. 張紅雨, 費立明, 王長亮, 等. 胰腺癌中CXCL12-CXCR4生物學軸與VEGF-C的表達及相關性研究. 中國現代普通外科進展, 2008, 11(4): 283-286.
16. 喻建, 曹軍. VEGF-C, CXCR4在胰腺癌中的表達與意義. 醫學新知雜志, 2008, 18(6): 342-343, 345.
17. 姚寶忠, 李良, 江鳴, 等. CD133和趨化因子受體4在胰腺癌中的表達及臨床相關性. 中華普通外科學文獻(電子版), 2017, 11(6): 375-379.
18. 許瑩, 潘振國, 李倩君, 等. GSK3β, CXCR4, MMP-2與胰腺癌侵襲和轉移的關系. 胃腸病學和肝病學雜志, 2016, 25(11): 1308-1311.
19. 徐鋒. SDF-1/CXCR4和TECK/CCR9與胰腺癌預后不良相關性研究. 天津: 天津醫科大學, 2013.
20. 王寶勝, 孟祥鵬, 劉臻, 等. 胰腺癌組織中SDF-1的表達與其臨床病理特征的關系. 現代腫瘤醫學, 2012, 20(3): 540-542.
21. 李玉軍, 李霞, 孫玲玲, 等. 胰腺癌CXCR-4, MMP-2, VEGF的表達及其與腫瘤生物學行為的關系. 中華胰腺病雜志, 2009, 9(5): 334-336.
22. 李輝, 呂麗紅, 張波, 等. CXCR-4在胰腺癌中的表達及臨床意義. 山東醫藥, 2008, 48(6): 64-65.
23. 符亮, 吳冬冰, 萬鴻興. 胰腺癌組織轉錄中介因子1及趨化因子受體-4的表達特點及臨床意義. 安徽醫藥, 2019, 23(9): 1842-1845.
24. 方德剛, 周光華. 人胰腺癌變組織中血管內皮生長因子微血管密度CXCR-4的表達及其意義. 山西醫藥雜志, 2011, 40(12): 1180-1181.
25. Zhang J, Liu C, Mo X, et al. Mechanisms by which CXCR4/CXCL12 cause metastatic behavior in pancreatic cancer. Oncol Lett, 2018, 15(2): 1771-1776.
26. Xu Q, Wang Z, Chen X, et al. Stromal-derived factor-1α/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer. Oncotarget, 2015, 6(7): 4717-4732.
27. Wehler T, Wolfert F, Schimanski CC, et al. Strong expression of chemokine receptor CXCR4 by pancreatic cancer correlates with advanced disease. Oncol Rep, 2006, 16(6): 1159-1164.
28. Wang Z, Ma Q, Li P, et al. Aberrant expression of CXCR4 and β-catenin in pancreatic cancer. Anticancer Res, 2013, 33(9): 4103-4110.
29. Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. Clin Cancer Res, 2000, 6(9): 3530-3535.
30. Liang JJ, Zhu S, Bruggeman R, et al. High levels of expression of human stromal cell-derived factor-1 are associated with worse prognosis in patients with stage Ⅱ pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev, 2010, 19(10): 2598-2604.
31. Jiang YM, Li G, Sun BC, et al. Study on the relationship between CXCR4 expression and perineural invasion in pancreatic cancer. Asian Pac J Cancer Prev, 2014, 15(12): 4893-4896.
32. Wu H, Zhu L, Zhang H, et al. Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma. PLoS One, 2015, 10(2): e116803.
33. Liao W, Wang H, Huang H, et al. CXCR4 expression predicts early liver recurrence and poor survival after resection of pancreatic adenocarcinoma. Clin Transl Gastroenterol, 2012, 3(9): e22.
34. Marechal R, Demetter P, Nagy N, et al. High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma. Br J Cancer, 2009, 100(9): 1444-1451.
35. Gebauer F, Tachezy M, Effenberger K, et al. Prognostic impact of CXCR4 and CXCR7 expression in pancreatic adenocarcinoma. J Surg Oncol, 2011, 104(2): 140-145.
36. 彭松慶. 血清基質金屬蛋白酶9和CC型趨化因子18對胰腺癌診斷性能評價. 中國衛生檢驗雜志, 2017, 27(23): 3417-3418.
37. 郭欣, 呂行, 謝嬌貴, 等. 趨化因子配體18表達水平對胰腺癌患者的預后價值. 中華肝膽外科雜志, 2015, 21(7): 474-477.
38. 孫聯康, 都大偉, 錢偉崐, 等. 趨化因子CXCL11激活NF-κB信號通路促進胰腺癌的侵襲轉移及上皮間質轉換. 西安交通大學學報(醫學版), 2019, 40(4): 501-505.
39. Zhang R, Liu Q, Peng J, et al. CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration. J Cancer, 2020, 11(9): 2371-2381.
40. Fan H, Wang W, Yan J, et al. Prognostic significance of CXCR7 in cancer patients: a meta-analysis. Cancer Cell Int, 2018, 18: 212.
41. Litman-Zawadzka A, ?ukaszewicz-Zaj?c M, Gryko M, et al. Serum chemokine CXCL8 as a better biomarker for diagnosis and prediction of pancreatic cancer than its specific receptor CXCR2, c-reactive protein, and classic tumor markers CA 19-9 and CEA. Pol Arch Intern Med, 2018, 128(9): 524-531.

Previous Article
Efficacy of 10 common used intrauterine devices: a network meta-analysis
Next Article
Application of Delphi method in clinical research of traditional Chinese medicine: a systematic review

Chinese Journal of Evidence-Based Medicine

Association between the expression of CXCL12/CXCR4 and pancreatic cancer: a meta-analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content