Iyer Prajish, Barreto Savio George, Sahoo Bikram, Chandrani Pratik, Ramadwar Mukta R, Shrikhande Shailesh V, Dutt Amit
Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai India.
Department of Gastrointestinal Surgery, Gastrointestinal Oncology, and Bariatric Surgery, Medanta Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Gurgaon, India.
Infect Agent Cancer. 2016 Mar 3;11:12. doi: 10.1186/s13027-016-0057-x. eCollection 2016.
We earlier proposed a genetic model for gallbladder carcinogenesis and its dissemination cascade. However, the association of gallbladder cancer and 'inflammatory stimulus' to drive the initial cascade in the model remained unclear. A recent study suggested infection with Salmonella can lead to changes in the host signalling pathways in gallbladder cancer.
We examined the whole exomes of 26 primary gall bladder tumour and paired normal samples for presence of 143 HPV (Human papilloma virus) types along with 6 common Salmonella serotypes (S. typhi Ty2, S. typhi CT18, S. typhimurium LT2, S. choleraesuis SCB67, S. paratyphi TCC, and S. paratyphi SPB7) using a computational subtraction pipeline based on the HPVDetector, we recently described. Based on our evaluation of 26 whole exome gallbladder primary tumours and matched normal samples: association of typhoidal Salmonella species were found in 11 of 26 gallbladder cancer samples, and non-typhoidal Salmonella species in 12 of 26 gallbladder cancer, with 6 samples were found co-infected with both.
We present the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal strains in gallbladder cancer. Salmonella infection in the chronic carrier state fits the role of the 'inflammatory stimulus' in the genetic model for gallbladder carcinogenesis that may play a role in gallbladder cancer analogous to Helicobacter pylori in gastric cancer.
我们之前提出了一种胆囊癌发生及其播散级联的遗传模型。然而,胆囊癌与模型中驱动初始级联的“炎症刺激”之间的关联仍不清楚。最近的一项研究表明,感染沙门氏菌可导致胆囊癌宿主信号通路发生变化。
我们使用我们最近描述的基于HPVDetector的计算减法流程,检查了26份原发性胆囊肿瘤及其配对正常样本的全外显子组,以检测143种人乳头瘤病毒(HPV)类型以及6种常见沙门氏菌血清型(伤寒沙门氏菌Ty2、伤寒沙门氏菌CT18、鼠伤寒沙门氏菌LT2、猪霍乱沙门氏菌SCB67、副伤寒沙门氏菌TCC和副伤寒沙门氏菌SPB7)。基于我们对26份全外显子组胆囊原发性肿瘤及匹配正常样本的评估:在26份胆囊癌样本中的11份中发现了伤寒沙门氏菌属的关联,在26份胆囊癌样本中的12份中发现了非伤寒沙门氏菌属的关联,有6份样本同时感染了这两种细菌。
我们提供了首个证据支持非伤寒沙门氏菌属与伤寒菌株在胆囊癌中的关联。慢性携带状态下的沙门氏菌感染符合胆囊癌发生遗传模型中“炎症刺激”的作用,其在胆囊癌中的作用可能类似于幽门螺杆菌在胃癌中的作用。