Are Gastric Cancer Resection Margin Proteomic Profiles More Similar to Those from Controls or Tumors?

A strategy for treating cancer is to surgically remove
the tumor together with a portion of apparently healthy tissue surrounding
it, the so-called “resection margin”, to minimize recurrence.
Here, we investigate whether the proteomic profiles from biopsies
of gastric cancer resection margins are indeed more similar to those
from healthy tissue than from cancer biopsies. To this end, we analyzed
biopsies using an offline MudPIT shotgun proteomic approach and performed
label-free quantitation through a distributed normalized spectral
abundance factor approach adapted for extracted ion chromatograms
(XICs). A multidimensional scaling analysis revealed that each of
those tissue-types is very distinct from each other. The resection
margin presented several proteins previously correlated with cancer,
but also other overexpressed proteins that may be related to tumor
nourishment and metastasis, such as collagen alpha-1, ceruloplasmin,
calpastatin, and E-cadherin. We argue that the resection margin plays
a key role in Paget’s “soil to seed” hypothesis,
that is, that cancer cells require a special microenvironment to nourish
and that understanding it could ultimately lead to more effective
treatments.

癌症治疗的一项经典策略是通过手术切除肿瘤及其周边外观正常的组织，即所谓的‘手术切缘（resection margin）’，以最大限度降低肿瘤复发风险。本研究旨在探究胃癌手术切缘活检样本的蛋白质组学特征，是否确实更贴近正常组织活检样本，而非癌组织活检样本。为此，我们采用离线多维蛋白质鉴定技术（MudPIT）鸟枪法蛋白质组学方法对活检样本进行分析，并通过适配提取离子色谱图（extracted ion chromatograms, XICs）的分布式归一化光谱丰度因子法完成无标记定量分析。多维尺度分析结果显示，三类组织样本彼此间均具有显著的特征差异。手术切缘样本中存在多种此前已被证实与癌症相关的蛋白质，同时还存在其他可能与肿瘤营养供给及转移相关的过表达蛋白，例如胶原蛋白α-1（collagen alpha-1）、铜蓝蛋白（ceruloplasmin）、钙蛋白酶抑制蛋白（calpastatin）以及E-钙粘蛋白（E-cadherin）。我们认为，手术切缘在佩吉特的‘种子与土壤’假说（Paget’s "soil to seed" hypothesis）中扮演着关键角色：即癌细胞需要特殊的微环境以获取营养，而阐明这一机制最终有望推动开发更有效的癌症治疗方案。