Knox Jennifer J, Jang Gun Ho, Grant Robert C, Zhang Amy, Ma Lucy, Elimova Elena, Jang Raymond, Moore Malcolm, Biagi James, Tehfe Mustapha, Ramjeesingh Ravi, Tsang Erica S, Holter Spring, Ramotar Stephanie, Hutchinson Shawn, Liang Sheng-Ben, Lungu Ilinca M, Moura Shari, Wang Yifan, Perera Sheron, Chan-Seng-Yue Michelle, Monajemzadeh Maryam, Aung Kyaw, Prince Rebecca, Romero Joan Miguel, Fuentes-Antras Jesus, Gonzalez Conchas Galileo A, Picardo Sarah, Gonzalez Ricardo, Ghai Sangeet, Khalili Korosh, Kyoung Kim Tae, Ng Karen, Bartlett John, Pugh Trevor J, Kalimuthu Sangeetha N, Fischer Sandra E, Wilson Julie M, Dodd Anna, Zogopoulos George, Grünwald Barbara T, Notta Faiyaz, Gallinger Steven, O'Kane Grainne M
Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, Canada.
Nat Commun. 2025 Jul 1;16(1):5919. doi: 10.1038/s41467-025-60808-z.
Integrated whole genome and transcriptome sequencing can unveil distinct molecular subgroups in pancreatic cancer (PDAC). The COMPASS trial (NCT02750657) enrolled 268 patients with advanced PDAC; patients were given either modified (m) FOLFIRINOX or Gemcitabine-nab-paclitaxel (GnP) as per physicians choice. Median follow-up is 52 months and median overall survival in those receiving mFOLFIRINOX is 10.6 months and 8.4 months for GnP. KRAS specific mutants and allelic states alone are not prognostic; however basal-like PDAC are more likely to harbour major imbalances in mutant KRAS (KRAS). In the presence of KRAS, pre-existing type II DM is more common. Distinct prognostic cohorts include homologous-recombination deficient PDAC, predictive of mFOLFIRINOX response. Basal-like PDAC and patients exhibiting evidence of systemic inflammation as annotated using the Gustave Roussy Immune Score are unique poor prognostic cohorts. The latter associates with low CD8 T cell infiltration while basal-like PDAC documents an inflamed tumour microenvironment.
全基因组和转录组联合测序能够揭示胰腺癌（PDAC）中不同的分子亚群。COMPASS试验（NCT02750657）纳入了268例晚期PDAC患者；根据医生的选择，患者接受改良（m）FOLFIRINOX方案或吉西他滨-纳米白蛋白结合型紫杉醇（GnP）治疗。中位随访时间为52个月，接受mFOLFIRINOX治疗患者的中位总生存期为10.6个月，接受GnP治疗患者的中位总生存期为8.4个月。仅KRAS特异性突变体和等位基因状态并无预后价值；然而，基底样PDAC更有可能存在突变型KRAS（KRAS）的主要失衡。在存在KRAS的情况下，既往存在的II型糖尿病更为常见。不同的预后队列包括同源重组缺陷型PDAC，其可预测mFOLFIRINOX反应。基底样PDAC以及使用古斯塔夫·鲁西免疫评分标注显示有全身炎症证据的患者是独特的预后不良队列。后者与低CD8 T细胞浸润相关，而基底样PDAC表现为肿瘤微环境炎症。
