Exploring the expression bar code of SAA variants for gastric cancer detection

Abstract

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.

Retracted: Arecoline induces epithelial‐mesenchymal transformation and promotes metastasis of oral cancer by SAA1 expression

“…SAA1, an acute‐phase protein, is mainly synthesized in the liver and is dramatically increased in inflammatory diseases 29 . High SAA1 expression has been reported in different types of cancers, including breast cancer, 30 renal cancer, 31 gastric cancer, 32 and others 33 . Masanori Takehara et al reported that pancreatic cancer cells induced de‐differentiation of adipocytes toward cancer‐associated adipocytes and that cancer‐associated adipocytes promoted the malignant characteristics of pancreatic cancer by SAA1 expression 34 .…”

Immune infiltration-associated serum amyloid A1 predicts favorable prognosis for hepatocellular carcinoma

“…In recent years, the importance of SAA in the malignant tumor has attracted much more attention. Some studies reported that serum SAA is a biomarker for some solid tumors, such as stomach, colon, pancreas, breast, and lung cancers, and that elevated SAA is also correlated with tumor stage[ 7 - 10 ]. SAA protein is mainly synthesized by the liver, and some literature has revealed its expression changes in liver diseases, such as liver injury and virus infection[ 11 ].…”

Extending the information content of the MALDI analysis of biological fluids via multi-million shot analysis

“…These modifications can be important for the phenotypic state of disease [17], and disease specific effects may be missed when studies rely on measurements at the level of protein families. For example, in Wu et al [18] different modifications of serum amyloid A (SAA) were shown to be associated with gastric cancer when compared to gastritis and healthy patients. Differences in relative amounts of truncated forms of SAA have been observed in acute vs chronic inflammation [19] as well as in type 2 diabetes mellitus patients compared to non-diabetics [20].…”