Piquemal David, Bruno Roman, Bournet Barbara, Ghiringhelli Francois, Noguier Florian, Canivet Cindy, Bertaut Aurélie, Pierrat Fabien, Evesque Ludovic, Gamez Amelia, Cros Jerome, Rederstorff Emilie, Petit Erwan, Adnet Johan, Saint Angélique, Drouillard Antoine, Kempf Emmanuelle, Soularue Emilie, Vincent Julie, Baumgaertner Isabelle, Hennequin Audrey, Tournigand Christophe, Lopez Trabada Ataz Daniel, Bengrine Leila, Lepage Come, Manfredi Sylvain, Afchain Pauline, Trouilloud Isabelle, Gagnaire Alice, LoConte Noelle K, Bachet Jean-Baptiste
Acobiom, Montpellier, France.
INSERM and CHU Toulouse, France.
J Gastrointest Oncol. 2023 Apr 29;14(2):997-1007. doi: 10.21037/jgo-22-946. Epub 2023 Apr 10.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, and chemotherapy is a key treatment for advanced PDAC. Gemcitabine chemotherapy is still an important component of treatment; however, there is no routine biomarker to predict its efficacy. Predictive tests may help clinicians to decide on the best first-line chemotherapy.
This study is a confirmatory study of a blood-based RNA signature, called the GemciTest. This test measures the expression levels of nine genes using real-time polymerase chain reaction (PCR) processes. Clinical validation was carried out, through a discovery and a validation phases, on 336 patients (mean 68.7 years; range, 37-88 years) for whom blood was collected from two prospective cohorts and two tumor biobanks. These cohorts included previously untreated advanced PDAC patients who received either a gemcitabine- or fluoropyrimidine-based regimen.
Gemcitabine-based treated patients with a positive GemciTest (22.9%) had a significantly longer progression-free survival (PFS) {5.3 2.8 months; hazard ratio (HR) =0.53 [95% confidence interval (CI): 0.31-0.92]; P=0.023} and overall survival (OS) [10.4 4.8 months; HR =0.49 (95% CI: 0.29-0.85); P=0.0091]. On the contrary, fluoropyrimidine-based treated patients showed no significant difference in PFS and OS using this blood signature.
The GemciTest demonstrated that a blood-based RNA signature has the potential to aid in personalized therapy for PDAC, leading to better survival rates for patients receiving a gemcitabine-based first-line treatment.
胰腺导管腺癌（PDAC）是一种致死率很高的癌症，化疗是晚期PDAC的关键治疗方法。吉西他滨化疗仍是治疗的重要组成部分；然而，尚无常规生物标志物可预测其疗效。预测性检测可能有助于临床医生决定最佳的一线化疗方案。
本研究是一项对基于血液的RNA标志物（称为GemciTest）的验证性研究。该检测使用实时聚合酶链反应（PCR）方法测量9个基因的表达水平。通过发现阶段和验证阶段，对336例患者（平均68.7岁；范围37 - 88岁）进行了临床验证，这些患者的血液来自两个前瞻性队列和两个肿瘤生物样本库。这些队列包括既往未接受过治疗的晚期PDAC患者，他们接受了基于吉西他滨或氟嘧啶的治疗方案。
基于吉西他滨治疗且GemciTest结果为阳性的患者（22.9%）无进展生存期（PFS）显著更长{5.3±2.8个月；风险比（HR） = 0.53 [95%置信区间（CI）：0.31 - 0.92]；P = 0.023}，总生存期（OS）也更长[10.4±4.8个月；HR = 0.49（95% CI：0.29 - 0.85）；P = 0.0091]。相反，基于氟嘧啶治疗的患者使用这种血液标志物在PFS和OS方面没有显著差异。
GemciTest表明，基于血液的RNA标志物有潜力辅助PDAC的个性化治疗，使接受基于吉西他滨一线治疗的患者生存率更高。
