Purpose: Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown.
Patients and methods: The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan-Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics.
Results: In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001).
Conclusion: The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.
Keywords: PD-L1; PTEN; biomarker; gastric cancer; molecular subtype.
© 2022 Cao et al.