Proteomic characteristics reveal the signatures and the risks of T1 colorectal cancer metastasis to lymph nodes

Abstract

The presence of lymph node metastasis (LNM) affects treatment strategy decisions in T1NxM0 colorectal cancer (CRC), but the currently used clinicopathological-based risk stratification cannot predict LNM accurately. In this study, we detected proteins in formalin-fixed paraffin-embedded (FFPE) tumor samples from 143 LNM-negative and 78 LNM-positive patients with T1 CRC and revealed changes in molecular and biological pathways by label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) and established classifiers for predicting LNM in T1 CRC. An effective 55-proteins prediction model was built by machine learning and validated in a training cohort (N=132) and two validation cohorts (VC1, N=42; VC2, N=47), achieved an impressive AUC of 1.00 in the training cohort, 0.96 in VC1 and 0.93 in VC2, respectively. We further built a simplified classifier with 9 proteins, and achieved an AUC of 0.824. The simplified classifier was performed excellent in two external validation cohorts. The expression patterns of 13 proteins were confirmed by immunohistochemistry, and the IHC score of 5 proteins were used to build a IHC predict model with an AUC of 0.825. RHOT2 silence significantly enhanced migration and invasion of colon cancer cells. Our study explored the mechanism of metastasis in T1 CRC and can be used to facilitate the individualized prediction of LNM in patients with T1 CRC, which may provide a guidance for clinical practice in T1 CRC.

Ribosomal Dysregulation in Metastatic Laryngeal Squamous Cell Carcinoma: Proteomic Insights and CX-5461’s Therapeutic Promise

“…Research has shown that ribosomes can modulate the rate of protein synthesis and play critical roles in cellular processes, such as proliferation, differentiation, apoptosis, and transformation [43,44]. Tumors may enhance ribosomal function to support their increased demand for active biosynthesis [45,46]. The overactivation of ribosomes in tumors is regulated by oncoproteins, noncoding RNAs, and various other factors [47].…”