Relationship between mismatch repair protein, RAS, BRAF, PIK3CA gene expression and clinicopathological characteristics in elderly colorectal cancer patients.
Relationship between mismatch repair protein, RAS, BRAF, PIK3CA gene expression and clinicopathological characteristics in elderly colorectal cancer patients.
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DOI：
10.12998/wjcc.v9.i11.2458
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发表时间：
2021-04-16
影响因子：
1.1
通讯作者：
Song X
中科院分区：
文献类型：
--
作者：
Fan JZ;Wang GF;Cheng XB;Dong ZH;Chen X;Deng YJ;Song X
结直肠癌（CRC）常见于老年患者。错配修复（MMR）蛋白缺失是导致结直肠癌的原因之一。RAS （KRAS/NRAS）、BRAF、PIK3CA基因是结直肠癌治疗中重要的基因靶点，与患者的预后和生存密切相关。然而，关于MMR、RAS、BRAF、PIK3CA的表达与结直肠癌患者临床病理特征的关系尚不清楚。分析MMR、RAS、BRAF、PIK3CA表达与结直肠癌临床病理特征的关系。共纳入327例老年结直肠癌患者，采用免疫组织化学检测MMR蛋白。采用实时定量聚合酶链反应检测RAS （KRAS/NRAS）、BRAF和PIK3CA基因。记录患者的临床病理资料，采用SPSS 19.0统计软件进行分析。在327例老年结直肠癌患者中，MMR蛋白丢失率为9.79%(32/327)，其中4种MMR蛋白（MSH2、MSH6、MLH1、PMS2）的缺失率分别为1.83%（6/327）、3.06%（10/327）、7.65%（25/327）、7.65%（25/327）。MMR蛋白缺失与性别、病理类型、肿瘤形态、分化程度、淋巴结转移无显著性差异（P < 0.05），而MMR蛋白缺失与肿瘤直径、肿瘤位置有显著性差异（P = 0.048/P = 0.000）。KRAS、NRAS、BRAF和PIK3CA基因在老年结直肠癌患者中的突变率分别为44.95%（147/327）、2.45%（8/327）、3.36%（11/327）和2.75% (9/327)；KRAS基因突变与肿瘤形态密切相关（P = 0.002），而与其他临床病理特征无关（P > 0.05）， NRAS基因突变与临床病理特征无显著差异（P > 0.05）。BRAF基因突变在病理类型、肿瘤位置、分化程度、淋巴结转移等方面存在显著差异（P < 0.05），但与性别、肿瘤大小、肿瘤形态无相关性（P < 0.05）。PIK3CA基因突变在上述临床病理特征上无显著差异（P < 0.05）。老年结直肠癌患者MMR蛋白缺失与KRAS、BRAF、PIK3CA基因突变差异有统计学意义（P = 0.044、P = 0.000、P = 0.003），而MMR蛋白缺失与NRAS基因突变差异无统计学意义（P < 0.05）。老年结直肠癌患者肿瘤主要位于右结肠，当肿瘤直径大于等于5 cm时，MMR蛋白缺失率较高；MLH1和PMS2基因缺失率较高；KRAS基因突变率高于NRAS、BRAF和PIK3CA基因，BRAF基因突变与临床病理特征有不同程度的相关性；当MMR蛋白缺失时，常出现BRAF和PIK3CA基因突变，KRAS基因突变率较低。
Colorectal cancer (CRC) is common in elderly patients. Mismatch repair (MMR) protein deletion is one of the causes of CRC. The RAS (KRAS/NRAS), BRAF, and PIK3CA genes are important gene targets in CRC treatment and are closely related to the prognosis and survival of patients. However, little is known regarding the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC patients. To analyze the relationship between the expression of MMR, RAS, BRAF, PIK3CA and the clinicopathological features in CRC. A total of 327 elderly patients with CRC were enrolled, and immuno-histochemistry was used to detect the MMR protein. Real-time quantitative polymerase chain reaction was used to detect the RAS (KRAS/NRAS), BRAF, and PIK3CA genes. The clinicopathological data of the patients were recorded and analyzed by SPSS 19.0 statistical software. In 327 elderly patients with CRC, the rate of MMR protein loss was 9.79% (32/327), and the deletion rate of four MMR proteins (MSH2, MSH6, MLH1, PMS2) was 1.83% (6/327), 3.06% (10/327), 7.65% (25/327), and 7.65% (25/327), respectively. There were no significant differences between MMR protein deletion and sex, pathological type, tumor morphology, differentiation degree or lymph node metastasis (P > 0.05), but there was a significant difference between MMR protein deletion and tumor diameter and tumor location (P = 0.048/P = 0.000). The mutation rates of the KRAS, NRAS, BRAF and PIK3CA genes in elderly CRC patients were 44.95% (147/327), 2.45% (8/327), 3.36% (11/327) and 2.75% (9/327), respectively; the KRAS gene mutation was closely related to tumor morphology (P = 0.002) but not to other clinicopathological features (P > 0.05), and there were no significant differences between NRAS gene mutation and clinicopathological features (P > 0.05). The BRAF gene mutation showed a significant difference in pathological type, tumor location, differentiation degree and lymph node metastasis (P < 0.05), but was not correlated with sex, tumor size and tumor morphology (P > 0.05). The PIK3CA gene mutation showed no significant differences in the above clinicopathological characteristics (P > 0.05). Significant differences were observed between MMR protein deletion and KRAS, BRAF, and PIK3CA gene mutations in elderly CRC patients (P = 0.044, P = 0.000, P = 0.003, respectively), but there was no significant difference between MMR protein deletion and NRAS mutation (P > 0.05). In elderly CRC patients, the tumor is mainly located in the right colon, and the deletion rate of MMR protein is higher when the tumor diameter is greater than or equal to 5 cm; the deletion rate of MLH1 and PMS2 is more common; the mutation rate of KRAS gene is higher than that of the NRAS, BRAF and PIK3CA genes, the BRAF gene mutation has different degrees of correlation with clinicopathological characteristics; when the MMR protein is deleted, the BRAF and PIK3CA gene mutations are often present, and the KRAS gene mutation rate is low.
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DOI：
10.1046/j.1432-1327.1999.00542.x
发表时间：
1999-08-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Besson, A;Robbins, SM;Yong, VW
通讯作者：
Yong, VW
影响因子：
10.3
作者：
Taieb, Julien;Le Malicot, Karine;Sinicrope, Frank A.
通讯作者：
Sinicrope, Frank A.
影响因子：
7.5
作者：
Rosty, Christophe;Young, Joanne P.;Buchanan, Daniel D.
通讯作者：
Buchanan, Daniel D.
影响因子：
7.4
作者：
Palomba G;Doneddu V;Cossu A;Paliogiannis P;Manca A;Casula M;Colombino M;Lanzillo A;Defraia E;Pazzola A;Sanna G;Putzu C;Ortu S;Scartozzi M;Ionta MT;Baldino G;Sarobba G;Capelli F;Sedda T;Virdis L;Barca M;Gramignano G;Budroni M;Tanda F;Palmieri G
通讯作者：
Palmieri G
影响因子：
2.8
作者：
Poulsen, Tim Svenstrup;de Oliveira, Douglas Vinicius Nogueira Perez;Hogdall, Estrid
通讯作者：
Hogdall, Estrid