AUTHOR=Du Juan , Qiu Xin  , Lu Changchang , Zhu Yahui , Kong Weiwei , Xu Mian , Zhang Xin , Tang Min , Chen Jun , Li Qi , Li Aimei  , He Jian  , Gu Qing , Wang Lei , Qiu Yudong , Liu Baorui 

TITLE=Molecular Landscape and Prognostic Biomarker Analysis of Advanced Pancreatic Cancer and Predictors of Treatment Efficacy of AG Chemotherapy

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.844527

DOI=10.3389/fonc.2022.844527

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>Although mutational analysis of pancreatic cancer has provided valuable clinical information, it has not significantly changed treatment prospects. The purpose of this study is to further investigate molecular alterations in locally advanced pancreatic cancer and identify predictors of the efficacy of nab-paclitaxel plus gemcitabine (AG) chemotherapy.</p></sec><sec><title>Experimental design</title><p>Tumor samples from 118 pancreatic cancer patients who received AG chemotherapy as first-line treatment were sequenced and genomic profile was generated. Molecular alterations and the involved signaling pathways were analyzed. Genes with a significant difference in mutation frequency between primary and metastatic tumors were identified, and prognostic-related mutant genes were screened using SPSS version 22.0.</p></sec><sec><title>Results</title><p>The most common altered genes in the patients were <italic>KRAS</italic> (94.9%), <italic>TP53</italic> (81.4%), <italic>CDKN2A</italic> (36.4%), and <italic>SMAD4</italic> (22.9%). The mutational frequencies of <italic>CDKN2B</italic> (14.8% vs. 0%, p = 0.001)<italic>, FAT3</italic> (7.4% vs. 0%, p = 0.041)<italic>, MTAP</italic> (13% vs. 1.6%, p = 0.023), and <italic>SMAD4</italic> (31.4% vs. 15.6%, p = 0.049) in metastatic tumors were significantly higher than that in primary tumors. <italic>TP35</italic> and <italic>KRAS</italic> mutations were significantly correlated with objective response rate, while <italic>EPHA7, RNF43</italic>, and <italic>HMGA2</italic> mutations were significantly correlated with disease control rate. Additionally, patients with <italic>TGFR2B, FGF23, EPHA7, SMARCA4, CARD11, ADGRA2, CCNE1</italic>, and <italic>ACVR2A</italic> alterations had a worse overall survival. Further, <italic>EPHA7, CARD11, NOTCH1, GATA6, ACVR2A</italic>, and <italic>HMGA2</italic> mutations indicated undesirable progression-free survival.</p></sec><sec><title>Conclusions</title><p><italic>CDKN2B</italic>, <italic>FAT3</italic>, <italic>MTAP</italic>, and <italic>SMAD4</italic> may be biomarkers that distinguish primary tumors from metastases. <italic>EPHA7</italic> mutation may serve as a prognostic biomarker to predict the treatment efficacy of AG chemotherapy in locally advanced pancreatic cancer.</p></sec>