Abstract

Long non-coding RNAs (lncRNAs) are crucial in controlling important aspects of tumor immunity. However, whether the expression pattern of lncRNAs in stomach adenocarcinoma (STAD) reflects tumor immunity is not fully understood. We screened differentially expressed lncRNAs (DElncRNAs) between high and low tumor mutation burden (TMB) STAD samples. Using the least absolute shrinkage and selection operator method, 33 DElncRNAs were chosen to establish a lncRNA-based signature classifier for predicting TMB levels. The accuracy of the 33-lncRNA-based signature classifier was 0.970 in the training set and 0.950 in the test set, suggesting the expression patterns of the 33 lncRNAs may be an indicator of TMB in STAD. Survival analysis showed that a lower classifier index reflected better prognosis for STAD patients, and the index showed correlation with expression of immune checkpoint molecules (PD1, PDL1, and CTLA4), tumor-infiltrating lymphocytes, and microsatellite instability. In conclusion, STAD samples with different tumor mutation burdens have different lncRNA expression patterns. The 33-lncRNA-based signature classifier index may be an indicator of TMB and is associated expression of immune checkpoints, tumor-infiltrating lymphocytes, and microsatellite instability.

Highlights

  • Stomach adenocarcinoma (STAD) accounts for 90% of gastric cancers (Hoffmann, 2015)

  • LncRNAs Differentially Expressed Between High- or Low-Tumor mutation burden (TMB) STAD Samples

  • We found that STAD patients with Microsatellite instability-high (MSI-H) have a lower Long non-coding RNAs (lncRNAs) base index (Figure 6B) than those with MSI-low or microsatellite stable (MSS)

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Summary

INTRODUCTION

Stomach adenocarcinoma (STAD) accounts for 90% of gastric cancers (Hoffmann, 2015). Surgical treatment remains the optimal treatment for early-stage STAD, but most STAD patients are diagnosed in an advanced stage (Song et al, 2017). ICIs are not effective for all STAD patients, so it would be helpful to identify indicators that can detect which patients are most likely to respond to ICIs. Tumor immunogenicity, expression of immune checkpoint molecules and tumor-infiltrating lymphocytes are indicators of ICI treatment efficacy (Schreiber et al, 2011; Galon and Bruni, 2019). Efficacy of ICIs in STAD cancer patients is connected to high TMB levels (Kim et al, 2014; Goodman et al, 2019; Samstein et al, 2019; Wang et al, 2019). Our present may provide a cost-effective way to identify STAD patients more likely to respond to ICIs, thereby helping personalize treatment

RESULTS
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DATA AVAILABILITY STATEMENT
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