研究动态
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对新辅助化疗抵抗性直肠癌恶性特征的探究,重点关注外肌层病变。

Exploration of Malignant Characteristics in Neoadjuvant Chemotherapy-Resistant Rectal Cancer, Focusing on Extramural Lesions.

发表日期:2023 Aug 07
作者: Shunsuke Kubota, Takuya Miura, Taiichi Wakiya, Tadashi Yoshizawa, Shintaro Goto, Hajime Morohashi, Yoshiyuki Sakamoto, Yota Tatara, Hiroshi Kijima, Kenichi Hakamada
来源: ANNALS OF SURGICAL ONCOLOGY

摘要:

肠直肠癌(RC)中,肠外腔内血管浸润(EMVI)和肿瘤沉积物(TD)是不良预后因素,特别是当对新辅助化疗(NAC)产生耐药性时。我们旨在确定与伴发EMVI和TD的NAC反应者和非反应者中差异性表达。我们从52例RC手术患者中提取了术后经NAC切除的标本,分为两组:残留EMVI和TD的病例(NAC耐药组)和没有残留的病例(NAC有效组)。进行了蛋白质组学分析,以确定两组中的差异蛋白质表达。为了验证结果,我们另外对包括58例RC手术患者的另一组进行了免疫组织化学实验。根据这些发现,比较了化疗敏感性和预后。NAC耐药组的3年无病生存率较NAC有效组低(p = 0.041)。NAC耐药组中的鉴别蛋白与硫代谢途径密切相关。在这些途径成分中,NAC耐药组中硒结合蛋白1(SELENBP1)的表达量较NAC有效组下降了三分之二以上。在另一RC组中的免疫组织化学实验证实了SELENBP1降低与较差的NAC敏感性之间的关系,无论是在NAC前活检还是NAC后手术标本中。此外,SELENBP1的降低与较低的3年无病生存率有关(p = 0.047)。我们确定了NAC反应者和非反应者之间差异表达的蛋白质之一,同时伴发EMVI和TD。据怀疑SELENBP1可能导致RC中的NAC耐药性和预后较差。© 2023年。作者。
Extramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD.From 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared.The NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047).We defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.© 2023. The Author(s).