Researchers from China identified 4 molecular subtypes of gastrointestinal stromal tumor (GIST) with distinct biological pathways and clinical characteristics based on long noncoding RNAs (lncRNAs). They published their results in PeerJ.

According to the authors, this lncRNA-based classification for GIST “may provide a molecular classification applicable to individual GIST” and has implications in terms of marker selection and predicting disease progression.

lncRNAs have been involved in the diagnosis and prognosis of many different types of cancer. However, reports on their potential role in predicting the prognosis of GIST have been limited. 


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To explore an lncRNA signature profile and its clinical relevance in GIST, the researchers used an lncRNA-mining approach. They performed a non-negative matrix factorization consensus algorithm in 61 patients with GIST to cluster lncRNA expression profiles.

The researchers identified 4 lncRNA molecular subtypes. They then performed comparative marker selection and a gene set enrichment analysis algorithm between these 4 subtypes.

lncRNA expression profiles clustered the GIST samples into small and large tumors. The small tumors were less than 5 mm in diameter, while the large tumors were greater than 5 mm in diameter. This is a fundamental index for the diagnosis of malignancy in GIST. 

The researchers identified 5 lncRNAs that were associated with tumor size: LRRC75A-AS1, HYMAI, NEAT1, XIST, and FTX. These lncRNAs could, therefore, serve as GIST malignancy biomarkers.

“Particularly, LRRC75A-AS1 was positively associated with tumor diameters,” the researchers wrote. They proposed that this could be an oncogene in GIST. Based on coexpression analysis, the researchers also suggested that chromosome region 17p11.2-p12 may contribute to the oncogenic process in GIST. 

Finally, the researchers found that lncRNA expression between female and male patients showed distinct profiles and that female patients had a favorable prognosis. This could be explained by the distinct pathways between female and male patients revealed by gene set enrichment analysis. The analysis also showed that malignant GIST was associated with several cancer metabolisms and cell cycle-associated pathways.

“Although the possible functions of many identified lncRNA genes need to be further investigated, our study of the lncRNA-based classification may provide an efficient classification tool for marker selection and clinical progression evaluation of GIST,” the researchers concluded.

Reference

Zhao Y, Liu X, Xiao K, et al. Clinicopathological value of long non-coding RNA profiles in gastrointestinal stromal tumor. PeerJ. 2021;9:e11946. doi:10.7717/peerj.11946