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P53 protein expression affected by TP53 polymorphism is associated with the biological behavior and prognosis of low rectal cancer.

ABSTRACT: Low rectal cancer is a subtype of colorectal cancer at a special anatomic site with distinct biological behavior. TP53 is one of the most important cancer suppressor genes, and its structural variation and abnormal expression has been revealed to be associated with multiple cancer types. However, to the best of our knowledge, the association of p53 protein expression with its gene polymorphism, biological behavior and prognosis in low rectal cancer has not been clarified. Therefore, the current study aimed to explore these associations. In the present study, 347 patients with low rectal cancer and 353 controls were enrolled. Kompetitive Allele-Specific Polymerase Chain Reaction was used to detect five polymorphic sites of the TP53 gene (rs1042522, rs12947788, rs1625895, rs2909430 and rs12951053), while immunohistochemistry was used to detect the protein expression of TP53. The associations between p53 protein expression and TP53 polymorphism, biological behavior and prognosis in low rectal cancer were systematically analyzed. In low rectal cancer, p53 protein expression was markedly higher in TP53 rs1042522 mutant carriers compared with that in other genotypes where expression was higher in poorly differentiated, III-IV phase and T3-4 phase tumors, and in III-IV phase female patients. The survival time of patients with low p53 protein expression was evidently longer in females, non-smokers and patients >60 years old. In summary, p53 protein expression was identified to be affected by TP53 rs1042522 polymorphism, and was associated with the biological behavior and prognosis of low rectal cancer. TP53 rs1042522 and the associated protein expression could be used as indicators for biological behavior and prognosis in low rectal cancer.

SUBMITTER: Zhang G

PROVIDER: S-EPMC6865730 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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p53 protein expression affected by TP53 polymorphism is associated with the biological behavior and prognosis of low rectal cancer.

Zhang Guangzhe G Xu Qian Q Wang Zeyang Z Sun Liping L Lv Zhi Z Liu Jingwei J Xing Chengzhong C Yuan Yuan Y

Oncology letters 20191018 6

Low rectal cancer is a subtype of colorectal cancer at a special anatomic site with distinct biological behavior. TP53 is one of the most important cancer suppressor genes, and its structural variation and abnormal expression has been revealed to be associated with multiple cancer types. However, to the best of our knowledge, the association of p53 protein expression with its gene polymorphism, biological behavior and prognosis in low rectal cancer has not been clarified. Therefore, the current ...[more]

PMID: 31788124

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Project description:Objectivep53 gene, as "the guardian of the genome", is the most widely studied tumor suppressor gene. Previous studies have shown that about 50 percent of tumors have P53 dysfunction. This article aims to retrospectively analyze the correlation between p53 rs1625895 polymorphism and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).MethodsPCR combined with Sanger sequencing were used to detect rs1625895 genotype in 384 DLBCL patients. The relationship between rs1625895 polymorphisms and the clinical characteristics, first-line therapeutic effects and the prognosis of the patients were analyzed.ResultsAmong all the patients, 2 (0.5%) patients with AA genotype, 34 (8.9%) patients with AG genotype and 348 (90.6%) patients with GG genotype were identified. The patients with different rs1625895 genotypes did not have any difference in terms of age, gender, B symptoms (developing any of the following symptoms: unexplained recurrent fever (often above 38 °C), night sweats, and unexplained weight loss of 10% within 6 months ), erythrocyte sedimentation rate (ESR), international prognostic index (IPI) and molecular subtype (P>0.05). The overall response rate (ORR) was 82.9% and 82.8% in AA/AG and GG, respectively. There was no significant difference between the first-line therapeutic effects of the two groups (P>0.05). And there was also no difference between A allele carriers and homozygous G allele carriers for the 5-year progressionfree survival rate (PFS) (71.8% vs. 62.3%, χ2=1.351, P=0.245) and 5-year overall survival rate (OS) (72.2% vs. 64.1%, χ2=1.267, P=0.260). But in the subgroup with Germinal Center B-cell (GCB) type, the patients carrying A allele for rs1625895 had an obviously longer PFS (91.7% vs. 72.7%, χ2=4.493, P=0.034) and OS (91.7% vs. 76.7%, χ2=4.246, P=0.039) compared with the patients homozygous for the G allele. As for the patients with non-GCB subtype, there was no significant difference in PFS and OS between different rs1625895 genotypes (P>0.05). According to whether the first-line regimen contained rituximab or not, the patients were divided into two groups treated with cyclophosphoramide, doxorubicin, vincristine and prednisone (CHOP) or with rituximab and CHOP (R-CHOP). But in both subgroups, there was no significant difference in the 5-year PFS and OS between the AA/AG and GG patients, too (P>0.05).ConclusionFor DLBCL patients receiving CHOP regimen chemotherapy in the first line, p53 rs1625895 cannot predict the clinical efficacy and prognosis of the patients, but in the patients with GCB subtype, this polymorphism may be a prognostic indicator.

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P53 protein expression affected by TP53 polymorphism is associated with the biological behavior and prognosis of low rectal cancer.

Publications

p53 protein expression affected by TP53 polymorphism is associated with the biological behavior and prognosis of low rectal cancer.

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