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

Abstract

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.

Tumor matrix protein collagen XIα1 in cancer

“…Similarly, resection margins from gastric carcinoma patients exhibit high colXIα1 levels 50 . Expression is also limited to stroma in colorectal cancer 20 .…”

A Time-Based and Intratumoral Proteomic Assessment of a Recurrent Glioblastoma Multiforme

“…These results corroborate on the postulation of the great variability, within the a single GBM, be it at the transcriptomic or proteomic level (6). Aquino et al used a Multidimensional Protein Identification Technology (MudPIT) (7) to compare the protein profile present in gastric cancer biopsies against its respective resection margin and healthy tissue acquired from endoscopic patients (8). The authors suggested that the resection margin “seemed more proteomically alike” to cancer than the healthy tissue (8).…”

“…Aquino et al used a Multidimensional Protein Identification Technology (MudPIT) (7) to compare the protein profile present in gastric cancer biopsies against its respective resection margin and healthy tissue acquired from endoscopic patients (8). The authors suggested that the resection margin “seemed more proteomically alike” to cancer than the healthy tissue (8). In another work from Aquino et al, a gastric cancer biopsy was sectioned into ten parts and then each part was analyzed by MudPIT.…”

Progress in the development of protein biomarkers of oesophageal and gastric cancers

“…The histological study of gastric cancer resection margins after surgery is often crucial to predicting the likelihood of tumour recurrence. But proteomic analysis of normal, resection margin and tumour tissue has recently indicated that each tissue type has its distinct protein profile . In this study, resection margins, even if histologically benign were found to express several proteins associated with tumour promotion that were absent in normal control tissue.…”

“…In this study, resection margins, even if histologically benign were found to express several proteins associated with tumour promotion that were absent in normal control tissue. This information was interpreted in the light of the 'seed and soil' tumour hypothesis and was thought to have implications for the recurrence of disease and or tumour progression after surgical resection [68].…”