Abstract:
Studies conducted worldwide in the last few decades have demonstrated that various high- and low-frequency inherited and somatic mutations play important roles in the pathogenesis of periampullary carcinoma. Owing to relatively inaccessible location and lack of specific early diagnostic signs, majority of periampullary tumors are difficult to manage. Limited chemotherapeutic options that are available are highly toxic and not very efficacious. CyclinD1, if found to be amplified in these malignancies, might become an important gene to be targeted for monoclonal antibody therapy. An analytical retrospective-prospective study was done on 35 patients of operable periampullary carcinoma, in Medical College, Kolkata from January 2019 to July 2020. After isolating DNA from tumor and corresponding normal tissue by Qiagen DNEasy kit, CyclinD1 amplification was assessed by RT-PCR using Taqman DNA copy number in the laboratory of Indian Statistical Institute. Survival analysis was done by Kaplan-Meier estimator and all statistical calculations performed through SPSS software. Six (17%) out of 35 patients were found to have > twofold amplifications of CyclinD1 gene. However, no positive correlation was found between CyclinD1 amplification and overall survival of the patients (p value 0.21). Positive correlation was not found in our study between CCND1 amplification and periampullary malignancy. However, a single large study conducted in Japan by Yamazaki showed reduced survival and higher metastasis in CyclinD1 positive periampullary carcinoma. So there is reasonable scope in future for large-scale population-based studies to establish similar association in our subcontinent as well.
摘要:
近几十年来在全球范围内进行的研究表明,各种高频和低频遗传和体细胞突变在壶腹周围癌的发病机理中起着重要作用。由于相对难以接近的位置和缺乏具体的早期诊断迹象,大多数壶腹周围肿瘤难以治疗。可用的有限的化疗选择是高毒性的并且不是非常有效的。如果发现CyclinD1在这些恶性肿瘤中扩增,可能成为单克隆抗体治疗的重要靶向基因。对35例可手术的壶腹周围癌患者进行了一项分析性回顾性前瞻性研究,在医学院,加尔各答从2019年1月到2020年7月。用QiagenDNEasy试剂盒从肿瘤和相应的正常组织中分离DNA后,在印度统计研究所的实验室中使用TaqmanDNA拷贝数通过RT-PCR评估CyclinD1扩增。通过Kaplan-Meier估计器进行生存分析,并通过SPSS软件进行所有统计计算。发现35例患者中有6例(17%)的CyclinD1基因扩增超过两倍。然而,CyclinD1扩增与患者总生存期之间未发现正相关(p值0.21).在我们的研究中,CCND1扩增与壶腹周围恶性肿瘤之间未发现正相关。然而,Yamazaki在日本进行的一项大型研究显示,CyclinD1阳性壶腹周围癌的生存率降低和转移增加。因此,未来大规模的基于人口的研究也有合理的范围,以在我们的次大陆建立类似的关联。