TY - JOUR
T1 - Proteomic signatures of diffuse and intestinal subtypes of gastric cancer
AU - Singh, Smrita
AU - Bhat, Mohd Younis
AU - Sathe, Gajanan
AU - Gopal, Champaka
AU - Sharma, Jyoti
AU - Madugundu, Anil K.
AU - Joshi, Neha S.
AU - Pandey, Akhilesh
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry‐based proteomics using tandem mass tags (TMT)‐based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two sub-types, which included gremlin1 (GREM1), bcl‐2‐associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma‐associated antigen 9 (MAGE‐A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE‐A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.
AB - Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry‐based proteomics using tandem mass tags (TMT)‐based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two sub-types, which included gremlin1 (GREM1), bcl‐2‐associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma‐associated antigen 9 (MAGE‐A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE‐A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.
KW - Diffuse gastric cancer
KW - Gastric cancer
KW - Intestinal gastric cancer
KW - Mass spectrometry
KW - Proteomics
KW - Signet ring cell carcinoma
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U2 - 10.3390/cancers13235930
DO - 10.3390/cancers13235930
M3 - Article
AN - SCOPUS:85119675881
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 23
M1 - 5930
ER -