TY - JOUR
T1 - Clinical and Genomic Features of Classical and Basal Transcriptional Subtypes in Pancreatic Cancer
AU - Singh, Harshabad
AU - Xiu, Joanne
AU - Kapner, Kevin S.
AU - Yuan, Chen
AU - Narayan, Raja R.
AU - Oberley, Matthew
AU - Farrell, Alex
AU - Surana, Rishi
AU - Huffman, Brandon M.
AU - Perez, Kimberly
AU - Cleary, James M.
AU - Jordan, Alexander C.
AU - Costa, Andressa Dias
AU - Williams, Hannah L.
AU - Raghavan, Srivatsan
AU - Weinberg, Benjamin
AU - Pishvaian, Michael J.
AU - Shroff, Rachna T.
AU - Goel, Sanjay
AU - Dougan, Stephanie K.
AU - Nowak, Jonathan A.
AU - Spetzler, David
AU - Sledge, George
AU - Wolpin, Brian M.
AU - Aguirre, Andrew J.
N1 - Publisher Copyright:
©2024 American Association for Cancer Research.
PY - 2024/11/1
Y1 - 2024/11/1
N2 - Purpose: Transcriptional profiling of pancreatic cancers has basal (SB). SC and SB tumors showed strong associations with defined two main transcriptional subtypes: classical and basal. histologic phenotypes and biopsy sites. SB tumors had higher rates Initial data suggest shorter survival for patients with basal tumors of KRAS, TP53, and ARID1A mutations, lower rates of SMAD4 and differing treatment sensitivity to FOLFIRINOX and gemci- mutation, and transcriptional evidence of epithelial-mesenchymal tabine plus nab-paclitaxel by transcriptional subtype. transition. Sixty of 77 cases (78%) maintained their transcriptional Experimental Design: We examined 8,743 patients with RNA subtype between temporally and/or spatially disparate lesions. In sequencing from pancreatic cancers performed at Caris Life Sciences. the outcome cohort, the SB subtype was associated with shorter Classical and basal subtypes were identified using purity independent overall survival time, regardless of whether they received FOL-subtyping algorithm on RNA sequencing, and two cohorts were FIRINOX or gemcitabine plus nab-paclitaxel as first-line chemo-analyzed: (i) the biomarker cohort included patients with complete therapy. The mutant KRAS allele type was prognostic of outcomes; molecular profiling data (n ¼ 7,250) and (ii) the outcome cohort however, this impact was restricted to SC tumors, whereas all included patients with metastatic disease with available survival out- mutant KRAS alleles had similarly poor outcomes in SB tumors. comes (n ¼ 5,335). A total of 3,842 patients were shared between the Conclusions: The SB subtype is a strong independent pretwo cohorts. Kaplan–Meier curves and Cox proportional hazards dictor of worse outcomes, regardless of the up-front chemo-regression were used to assess patient survival. therapy regimen used. Clinical trials should further investigate Results: In the biomarker cohort, 3,063 tumors (42.2%) were pancreatic cancer transcriptional subtypes as a prognostic and strongly classical (SC) and 2,015 tumors (27.8%) were strongly predictive biomarker.
AB - Purpose: Transcriptional profiling of pancreatic cancers has basal (SB). SC and SB tumors showed strong associations with defined two main transcriptional subtypes: classical and basal. histologic phenotypes and biopsy sites. SB tumors had higher rates Initial data suggest shorter survival for patients with basal tumors of KRAS, TP53, and ARID1A mutations, lower rates of SMAD4 and differing treatment sensitivity to FOLFIRINOX and gemci- mutation, and transcriptional evidence of epithelial-mesenchymal tabine plus nab-paclitaxel by transcriptional subtype. transition. Sixty of 77 cases (78%) maintained their transcriptional Experimental Design: We examined 8,743 patients with RNA subtype between temporally and/or spatially disparate lesions. In sequencing from pancreatic cancers performed at Caris Life Sciences. the outcome cohort, the SB subtype was associated with shorter Classical and basal subtypes were identified using purity independent overall survival time, regardless of whether they received FOL-subtyping algorithm on RNA sequencing, and two cohorts were FIRINOX or gemcitabine plus nab-paclitaxel as first-line chemo-analyzed: (i) the biomarker cohort included patients with complete therapy. The mutant KRAS allele type was prognostic of outcomes; molecular profiling data (n ¼ 7,250) and (ii) the outcome cohort however, this impact was restricted to SC tumors, whereas all included patients with metastatic disease with available survival out- mutant KRAS alleles had similarly poor outcomes in SB tumors. comes (n ¼ 5,335). A total of 3,842 patients were shared between the Conclusions: The SB subtype is a strong independent pretwo cohorts. Kaplan–Meier curves and Cox proportional hazards dictor of worse outcomes, regardless of the up-front chemo-regression were used to assess patient survival. therapy regimen used. Clinical trials should further investigate Results: In the biomarker cohort, 3,063 tumors (42.2%) were pancreatic cancer transcriptional subtypes as a prognostic and strongly classical (SC) and 2,015 tumors (27.8%) were strongly predictive biomarker.
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U2 - 10.1158/1078-0432.CCR-24-1164
DO - 10.1158/1078-0432.CCR-24-1164
M3 - Article
C2 - 39283131
AN - SCOPUS:85208451697
SN - 1078-0432
VL - 30
SP - 4932
EP - 4942
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -