Browsing by Author "Rashid, Asif"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Association of Aflatoxin and Gallbladder Cancer
    (2017) Koshiol, Jill; Gao, Yu-Tang; Dean, Michael; Egner, Patricia; Nepal, Chirag; Jones, Kristine; Wang, Bingsheng; Rashid, Asif; Luo, Wen; Ferreccio Readi, Catterina; Van Dyke, Alison; Malasky, Michael; Shen, Ming-Chang; Zhu, Bin; Andersen, Jesper B.; Hildesheim, Allan; Hsing, Ann W.; Groopman, John
  • No Thumbnail Available
    Item
    Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies
    (2016) Koshiol, Jill; Castro, Felipe; Kemp, Troy J.; Gao, Yu-Tang; Carlos Roa, Juan; Wang, Bingsheng; Nogueira, Leticia; Carlos Araya, Juan; Shen, Ming-Chang; Rashid, Asif; Hsing, Ann W.; Hildesheim, Allan; Ferreccio, Catterina; Pfeiffer, Ruth M.; Pinto, Ligia A.
    Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate the findings in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p <0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9-790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C -reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8-18.4) for CXCL10 to 58.2 (95% CI: 12.4-273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC. Published by Elsevier Ltd.
  • No Thumbnail Available
    Item
    Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes
    (2021) Nepal, Chirag; Zhu, Bin; O'Rourke, Colm J.; Bhatt, Deepak Kumar; Lee, Donghyuk; Song, Lei; Wang, Difei; Van Dyke, Alison L.; Choo-Wosoba, Hyoyoung; Liu, Zhiwei; Hildesheim, Allan; Goldstein, Alisa M.; Dean, Michael; LaFuente-Barquero, Juan; Lawrence, Scott; Mutreja, Karun; Olanich, Mary E.; Bermejo, Justo Lorenzo; Ferreccio, Catterina; Roa, Juan Carlos; Rashid, Asif; Hsing, Ann W.; Gao, Yu-Tang; Chanock, Stephen J.; Araya, Juan Carlos; Andersen, Jesper B.; Koshiol, Jill
    Background & Aims: Gallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterise GBC and explore molecular subtypes associated with patient survival. Methods: We profiled the mutational landscape of GBC tumours (whole-exome sequencing on 92, targeted sequencing on 98, in total 190 patients). In a subset (n = 45), we interrogated the matched transcriptomes, DNA methylomes, and somatic copy number alterations. We explored molecular subtypes identified through clustering tumours by genes whose expression was associated with survival in 47 tumours and validated subtypes on 34 publicly available GBC cases. Results: Exome analysis revealed TP53was themostmutated gene. The overallmutation ratewas low(median 0.82Mut/Mb). APOBECmediated mutational signatures were more common in tumours with higher mutational burden. Aflatoxin-related signatures tended to be highly clonal (present in >-50% of cancer cells). Transcriptome-wide survival association analysis revealed a 95gene signature that stratified all GBC patients into 3 subtypes that suggested an association with overall survival post-resection. The 2 poor-survival subtypes were associated with adverse clinicopathologic features (advanced stage, pN1, pM1), immunosuppressive micro-environments (myeloid-derived suppressor cell accumulation, extensive desmoplasia, hypoxia) and T cell dysfunction, whereas the good-survival subtype showed the opposite features. Conclusion: These data suggest that the tumour microenvironment and immune profiles could play an important role in gallbladder carcinogenesis and should be evaluated in future clinical studies, along with mutational profiles. Lay summary: Gallbladder cancer is highly fatal, and its causes are poorly understood. We evaluated gallbladder tumours to see if there were differences between tumours in genetic information such as DNA and RNA. We found evidence of aflatoxin exposure in these tumours, and immune cells surrounding the tumours were associated with survival. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
  • Thumbnail Image
    Item
    RNA. sequencing-based analysis of gallbladder cancer reveals the importance of the liver X. receptor and lipid metabolism in gallbladder cancer
    (2016) Zuo, Mingxin; Rashid, Asif; Wang, Ying; Jain, Apurva; Li, Donghui; Behari, Anu; Kapoor, Vinay Kumar; Koay, Eugene J.; Chang, Ping; Roa Strauch, Juan Carlos Enrique; Vauthey, Jean Nicholas; Li, Yanan; Espinoza, Jaime A.; Javle, Milind
  • No Thumbnail Available
    Item
    TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern
    (2024) Pehlivanoglu, Burcin; Araya, Juan Carlos; Lawrence, Scott; Roa, Juan Carlos; Balci, Serdar; Andersen, Jesper B.; Rashid, Asif; Hsing, Ann W.; Zhu, Bin; Gao, Yu-Tang; Koshiol, Jill; Adsay, Volkan
    A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPPBRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastropancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubularspindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.