Spolverato Gaya, Fassan Matteo, Scarpa Melania, Stepanyan Astghik, De Simoni Ottavia, Scognamiglio Federico, Chiminazzo Valentina, De Nardi Clarissa, Tamponi Giulia, Negro Silvia, Angriman Imerio, Kotsafti Andromachi, Ruffolo Cesare, Vignotto Chiara, Zizzo Maurizio, Marchegiani Francesco, Facci Luca, Bergamo Francesca, Brignola Stefano, Businello Gianluca, Guzzardo Vincenza, Dal Santo Luca, Salmaso Roberta, Ceccon Carlotta, Massani Marco, Pozza Anna, Cataldo Ivana, Stecca Tommaso, Dei Tos Angelo Paolo, Zagonel Vittorina, Pilati Pierluigi, Franzato Boris, Scapinello Antonio, Pirozzolo Giovanni, Recordare Alfonso, Merenda Roberto, Bordignon Giovanni, Laurino Licia, Guerriero Silvio, Romiti Chiara, Portale Giuseppe, Cipollari Chiara, Candioli Salvatore, Gavagna Laura, Pozza Giulia, Godina Mario, Mondi Isabella, Noaro Giulia, Ortenzi Monica, Guerrieri Mario, Tagliente Giovanni, Tomassi Monica, Tedeschi Umberto, Porzionato Andrea, Agostini Marco, Maretto Isacco, Bao Quoc Riccardo, Cavallin Francesco, Di Camillo Barbara, Bardini Romeo, Castagliuolo Ignazio, Pucciarelli Salvatore, Scarpa Marco
UOC Chirurgia Generale 3, Azienda Ospedale-Università Padova, Padua, Italy.
Department of Medicine DIMED, University of Padua, Padua, Italy.
Br J Surg. 2023 Oct 10;110(11):1490-1501. doi: 10.1093/bjs/znad219.
Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer.
Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series.
In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8β expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa.
Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.
年轻患者的结肠癌常与遗传综合征相关；然而，在早发性直肠癌中，很少观察到这些基因的突变。本研究的目的是分析早发性直肠癌局部免疫微环境的特征和突变模式。
对帕多瓦大学医院直肠癌系列中的常见突变基因进行分析。比较了来自癌症基因组图谱（“TCGA”）队列中的突变频率和免疫基因表达，并在直肠癌腺癌治疗1和2（“IMMUNOREACT”）系列中评估了直肠癌旁健康直肠黏膜中的免疫细胞浸润水平。
在作者的系列研究中，早发性和晚发性直肠癌之间BRAF、KRAS和NRAS的突变频率以及微卫星不稳定性频率没有差异。在癌症基因组图谱系列中，在年轻和老年患者之间突变频率差异最大的基因中，有7个基因参与免疫反应且早发性直肠癌中CD６９、CD3和CD8β表达较低。在直肠癌腺癌治疗1和2系列的免疫微环境中，年轻患者的CD4+T细胞比例较低，但直肠黏膜中调节性T细胞浸润较高。
早发性直肠癌很少与常见的遗传综合征相关。肿瘤微环境的特征是损害局部免疫监视机制的突变频率高以及免疫编辑相关基因的低表达。CD4 T细胞数量持续较低且调节性T细胞数量较高表明免疫监视机制失衡。
