Expression of alpha B-crystallin in gastric cancer tissue and the influence of chemotherapeutics on expression of CRYAB mRNA_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XIAO Guo ¹ ,  JIANG Huaiwu ^1,2 , XU Liang ¹ , MING Rui ² , MA Bo ³

1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000,P. R. China;
2. Department of Gastrointestinal Surgery, Sichuan Mianyang 404 Hospital, Mianyang, Sichuan 621000, P. R. China;
3. Department of Pathology, Sichuan Mianyang 404 Hospital, Mianyang, Sichuan 621000, P. R. China;

Corresponding author：

JIANG Huaiwu, Email: Jhuaiwu@163.com

Keywords：

gastric cancer; alpha B-crystallin; neoadjuvant chemotherapy; chemotherapy resistance; immunohistochemistry method

DOI：

10.7507/1007-9424.202005025

Video：

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Objective To explore the expression of alpha B-crystallin (CRYAB) in human gastric cancer tissue and the influence of chemotherapeutics on expression of CRYAB mRNA.Methods ① The gastric cancer tissues and corresponding adjacent tissues of 76 patients underwent radical resection from April 2018 to March 2020 in The First Affiliated Hospital of Southwest Medical University and the Sichuan Mianyang 404 Hospital were collected, the expression of CRYAB protein in the gastric cancer tissues and corresponding adjacent tissues of 76 patients with gastric cancer were detected by immunohistochemistry SP technique. The relation between the expression of CRYAB protein and clinicopathologic features was analyzed. ② Twenty-one gastric tissues of patients accepted neoadjuvant chemotherapy and 26 gastric tissues of patients with no neoadjuvant chemotherapy in the The First Affiliated Hospital of Southwest Medical University were collected from November 2018 to March 2020, the expression of CRYAB mRNA was detected by real time-PCR.Results The expression of CRYAB protein in gastric cancer tissues was positive in 51 cases (67.1%) and in the corresponding adjacent tissues was positive in 32 cases (42.1%), the positive rate was higher in gastric cancer tissues (χ²=9.581, P=0.002). The over-expression of CRYAB protein in the gastric cancer tissues was correlated with the TNM stage, Borrmann typing, degree of differentiation, lymph node metastasis, depth of invasion of the patients, and Lauren classification (P<0.05), but not correlated with the age, gender, tumor sitation, and diameter (P>0.05). The expression of CRYAB mRNA in the gastric cancer tissues with neoadjuvant chemotherapy was significantly higher than that in the gastric cancer tissues without neoadjuvant chemotherapy (t=8.37, P<0.001).Conclusions The over-expression of CRYAB protein is closely related to the invasion and progression of gastric cancer, they may be involved in the progression of gastric cancer and play a crucial role. Moreover, the expression of CRYAB mRNA increases after chemotherapy, it suggests that chemotherapy drugs can activate the self-protection mechanism of tumor cells to some extent, and influence the effect of chemotherapy by increasing expression of CRYAB protein.

Citation： XIAO Guo, JIANG Huaiwu, XU Liang, MING Rui, MA Bo. Expression of alpha B-crystallin in gastric cancer tissue and the influence of chemotherapeutics on expression of CRYAB mRNA. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(2): 212-218. doi: 10.7507/1007-9424.202005025 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3.	Chen S, Pan S, Wu H, et al. ICAM1 regulates the development of gastric cancer and may be a potential biomarker for the early diagnosis and prognosis of gastric cancer. Cancer Manag Res, 2020, 12: 1523-1534.
4.	Song Z, Wu Y, Yang J, et al. Progress in the treatment of advanced gastric cancer. Tumour Biol, 2017, 39(7): 1010428317714626.
5.	Digklia A, Wagner AD. Advanced gastric cancer: current treatment landscape and future perspectives. World J Gastroenterol, 2016, 22(8): 2403-2414.
6.	吴永娜, 任程晖, 张磊, 等. αβ-晶状体蛋白在肿瘤中的研究进展. 兰州大学学报 (医学版), 2017, 43(5): 68-72.
7.	张峰, 赵达, 侯小明, 等. 慢病毒介导的αB-晶状体蛋白基因沉默对胃癌细胞SGC-7901增殖和迁移能力的影响. 兰州大学学报 (医学版), 2017, 43(2): 1-6.
8.	Taba K, Kuramitsu Y, Ryozawa S, et al. Heat-shock protein 27 is phosphorylated in gemcitabine-resistant pancreatic cancer cells. Anticancer Res, 2010, 30(7): 2539-2543.
9.	Zhang J, Liu J, Wu J, et al. Progression of the role of CRYAB in signaling pathways and cancers. Onco Targets Ther, 2019, 12: 4129-4139.
10.	Mousa GY, Trevithick JR. Differentiation of rat lens epithelial cells in tissue culture. Ⅱ. Effects of cytochalasins B and D on actin organization and differentiation. Dev Biol, 1977, 60(1): 14-25.
11.	Bennardini F, Wrzosek A, Chiesi M. Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments. Circ Res, 1992, 71(2): 288-294.
12.	Atomi Y, Yamada S, Strohman R, et al. Alpha B-crystallin in skeletal muscle: purification and localization. J Biochem, 1991, 110(5): 812-822.
13.	Nicoletti JG, White BG, Miskiewicz EI, et al. Induction of expression and phosphorylation of heat shock protein B5 (CRYAB) in rat myometrium during pregnancy and labour. Reproduction, 2016, 152(1): 69-79.
14.	Wittig R, Nessling M, Will RD, et al. Candidate genes for cross-resistance against DNA-damaging drugs. Cancer Res, 2002, 62(22): 6698-6705.
15.	Kase S, Parikh JG, Rao NA. Expression of heat shock protein 27 and alpha-crystallins in human retinoblastoma after chemoreduction. Br J Ophthalmol, 2009, 93(4): 541-544.
16.	Bao J, Ni Y, Qin H, et al. Rab27b is a potential predictor for metastasis and prognosis in colorectal cancer. Gastroenterol Res Pract, 2014, 2014: 913106.
17.	Iwaki T, Kume-Iwaki A, Liem RK, et al. Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander’s disease brain. Cell, 1989, 57(1): 71-78.
18.	Wang X, Osinska H, Klevitsky R, et al. Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res, 2001, 89(1): 84-91.
19.	Berry V, Francis P, Reddy MA, et al. Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet, 2001, 69(5): 1141-1145.
20.	Stronach EA, Sellar GC, Blenkiron C, et al. Identification of clinically relevant genes on chromosome 11 in a functional model of ovarian cancer tumor suppression. Cancer Res, 2003, 63(24): 8648-8655.
21.	Mineva I, Gartner W, Hauser P, et al. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing. Cell Stress Chaperones, 2005, 10(3): 171-184.
22.	Liu RZ, Li S, Garcia E, et al. Association between cytoplasmic CRABP2, altered retinoic acid signaling, and poor prognosis in glioblastoma. Glia, 2016, 64(6): 963-976.
23.	Voduc KD, Nielsen TO, Perou CM, et al. αB-crystallin expression in breast cancer is associated with brain metastasis. NPJ Breast Cancer, 2015, 1: 15014.
24.	Guo Z, Song J, Hao J, et al. M2 macrophages promote NSCLC metastasis by upregulating CRYAB. Cell Death Dis, 2019, 10(6): 377.
25.	Li Q, Wang Y, Lai Y, et al. HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling. PLoS One, 2017, 12(8): e0182588.
26.	许里, 徐新宇, 林振中. CRYAB在喉癌中的表达变化及临床意义. 南京医科大学学报 (自然科学版), 2016, 36(9): 1095-1100.
27.	朱骏, 冯颖, 张峰, 等. 晶状体蛋白αb在结直肠癌组织中的表达及其临床意义. 中国普外基础与临床杂志, 2015, 22(11): 1332-1337.
28.	Qin H, Ni Y, Tong J, et al. Elevated expression of CRYAB predicts unfavorable prognosis in non-small cell lung cancer. Med Oncol, 2014, 31(8): 142.
29.	Volkmann J, Reuning U, Rudelius M, et al. High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells. Int J Cancer, 2013, 132(12): 2820-2832.
30.	Wang SN, Luo S, Liu C, et al. miR-491 inhibits osteosarcoma lung metastasis and chemoresistance by targeting αB-crystallin. Mol Ther, 2017, 25(9): 2140-2149.
31.	Arrigo AP, Simon S, Gibert B, et al. Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett, 2007, 581(19): 3665-3674.
32.	Kori M, Yalcin Arga K. Potential biomarkers and therapeutic targets in cervical cancer: Insights from the meta-analysis of transcriptomics data within network biomedicine perspective. PLoS One, 2018, 13(7): e0200717.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. Chen S, Pan S, Wu H, et al. ICAM1 regulates the development of gastric cancer and may be a potential biomarker for the early diagnosis and prognosis of gastric cancer. Cancer Manag Res, 2020, 12: 1523-1534.
4. Song Z, Wu Y, Yang J, et al. Progress in the treatment of advanced gastric cancer. Tumour Biol, 2017, 39(7): 1010428317714626.
5. Digklia A, Wagner AD. Advanced gastric cancer: current treatment landscape and future perspectives. World J Gastroenterol, 2016, 22(8): 2403-2414.
6. 吴永娜, 任程晖, 张磊, 等. αβ-晶状体蛋白在肿瘤中的研究进展. 兰州大学学报 (医学版), 2017, 43(5): 68-72.
7. 张峰, 赵达, 侯小明, 等. 慢病毒介导的αB-晶状体蛋白基因沉默对胃癌细胞SGC-7901增殖和迁移能力的影响. 兰州大学学报 (医学版), 2017, 43(2): 1-6.
8. Taba K, Kuramitsu Y, Ryozawa S, et al. Heat-shock protein 27 is phosphorylated in gemcitabine-resistant pancreatic cancer cells. Anticancer Res, 2010, 30(7): 2539-2543.
9. Zhang J, Liu J, Wu J, et al. Progression of the role of CRYAB in signaling pathways and cancers. Onco Targets Ther, 2019, 12: 4129-4139.
10. Mousa GY, Trevithick JR. Differentiation of rat lens epithelial cells in tissue culture. Ⅱ. Effects of cytochalasins B and D on actin organization and differentiation. Dev Biol, 1977, 60(1): 14-25.
11. Bennardini F, Wrzosek A, Chiesi M. Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments. Circ Res, 1992, 71(2): 288-294.
12. Atomi Y, Yamada S, Strohman R, et al. Alpha B-crystallin in skeletal muscle: purification and localization. J Biochem, 1991, 110(5): 812-822.
13. Nicoletti JG, White BG, Miskiewicz EI, et al. Induction of expression and phosphorylation of heat shock protein B5 (CRYAB) in rat myometrium during pregnancy and labour. Reproduction, 2016, 152(1): 69-79.
14. Wittig R, Nessling M, Will RD, et al. Candidate genes for cross-resistance against DNA-damaging drugs. Cancer Res, 2002, 62(22): 6698-6705.
15. Kase S, Parikh JG, Rao NA. Expression of heat shock protein 27 and alpha-crystallins in human retinoblastoma after chemoreduction. Br J Ophthalmol, 2009, 93(4): 541-544.
16. Bao J, Ni Y, Qin H, et al. Rab27b is a potential predictor for metastasis and prognosis in colorectal cancer. Gastroenterol Res Pract, 2014, 2014: 913106.
17. Iwaki T, Kume-Iwaki A, Liem RK, et al. Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander’s disease brain. Cell, 1989, 57(1): 71-78.
18. Wang X, Osinska H, Klevitsky R, et al. Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res, 2001, 89(1): 84-91.
19. Berry V, Francis P, Reddy MA, et al. Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet, 2001, 69(5): 1141-1145.
20. Stronach EA, Sellar GC, Blenkiron C, et al. Identification of clinically relevant genes on chromosome 11 in a functional model of ovarian cancer tumor suppression. Cancer Res, 2003, 63(24): 8648-8655.
21. Mineva I, Gartner W, Hauser P, et al. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing. Cell Stress Chaperones, 2005, 10(3): 171-184.
22. Liu RZ, Li S, Garcia E, et al. Association between cytoplasmic CRABP2, altered retinoic acid signaling, and poor prognosis in glioblastoma. Glia, 2016, 64(6): 963-976.
23. Voduc KD, Nielsen TO, Perou CM, et al. αB-crystallin expression in breast cancer is associated with brain metastasis. NPJ Breast Cancer, 2015, 1: 15014.
24. Guo Z, Song J, Hao J, et al. M2 macrophages promote NSCLC metastasis by upregulating CRYAB. Cell Death Dis, 2019, 10(6): 377.
25. Li Q, Wang Y, Lai Y, et al. HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling. PLoS One, 2017, 12(8): e0182588.
26. 许里, 徐新宇, 林振中. CRYAB在喉癌中的表达变化及临床意义. 南京医科大学学报 (自然科学版), 2016, 36(9): 1095-1100.
27. 朱骏, 冯颖, 张峰, 等. 晶状体蛋白αb在结直肠癌组织中的表达及其临床意义. 中国普外基础与临床杂志, 2015, 22(11): 1332-1337.
28. Qin H, Ni Y, Tong J, et al. Elevated expression of CRYAB predicts unfavorable prognosis in non-small cell lung cancer. Med Oncol, 2014, 31(8): 142.
29. Volkmann J, Reuning U, Rudelius M, et al. High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells. Int J Cancer, 2013, 132(12): 2820-2832.
30. Wang SN, Luo S, Liu C, et al. miR-491 inhibits osteosarcoma lung metastasis and chemoresistance by targeting αB-crystallin. Mol Ther, 2017, 25(9): 2140-2149.
31. Arrigo AP, Simon S, Gibert B, et al. Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett, 2007, 581(19): 3665-3674.
32. Kori M, Yalcin Arga K. Potential biomarkers and therapeutic targets in cervical cancer: Insights from the meta-analysis of transcriptomics data within network biomedicine perspective. PLoS One, 2018, 13(7): e0200717.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of alpha B-crystallin in gastric cancer tissue and the influence of chemotherapeutics on expression of CRYAB mRNA

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