The prognosis of the poorly differentiated subtype of thyroid carcinoma (THCA) is less favorable due to its aggressive nature, which also increases the likelihood of metastasis to distant organs. The present study aimed to assess the potential application of protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a molecular biomarker for early identification and prognosis prediction in THCA. The Cancer Genome Atlas (TCGA) database was used to identify genes associated with prognosis and differentially expressed genes in THCA. Additionally, TCGA data were used to analyze the differential expression of the PPP1R3G gene in THCA tissues compared with that in normal tissues. Immunohistochemistry was used for further confirmation of these findings. A prognostic significance analysis of the PPP1R3G gene was performed in patients diagnosed with THCA using Cox regression models. Both univariate and multivariate approaches were used, incorporating clinical information obtained from the patients. Moreover, to gain insights into the molecular mechanisms underlying the regulatory role of the PPP1R3G gene in THCA, a functional enrichment analysis performed. An assessment of the levels of immune cell infiltration in patients with THCA was also performed and their correlation with the expression level of PPP1R3G gene was assessed. The mRNA and protein levels of PPP1R3G were revealed to be higher in THCA tissues compared with that of noncancerous thyroid tissues. Moreover, there were significant associations between the expression of PPP1R3G in THCA and factors such as sex, histological type, pathological node stage, pathological stage, extrathyroidal extension and overall survival (OS). Univariate and multivariate Cox regression analyses revealed that the independent prognostic value of PPP1R3G could be used to predict the OS of patients with THCA. The outcomes obtained from functional enrichment analysis indicated a potential involvement of PPP1R3G in regulation of biological processes such as keratinization, and differentiation of keratinocytes and epidermal cells. Additionally, an association was demonstrated between the expression levels of PPP1R3G gene and several immune cells present within the tumor microenvironment of the thyroid. In conclusion, PPP1R3G has the potential to serve as a prognostic indicator for patients diagnosed with THCA, and may also be considered a promising target for therapeutic interventions in THCA.

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