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TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition.

ABSTRACT: The mortality rate of pancreatic adenocarcinoma is high, and the effect of traditional treatment is unsatisfactory, thus novel biomarkers are required. Although the important role of tetratricopeptide repeat domain 22 (TTC22) in colon cancer is well established, its precise role in pancreatic cancer remains unclear and requires further investigation. Pan-cancer analysis and single-cell sequencing revealed TTC22 was differentially expressed in various tumors, especially in pancreatic adenocarcinoma. Additionally, clinical data for pancreatic cancer showed a negative association between TTC22 expression and clinical parameters, including survival prognosis. The correlation between TTC22 and immune infiltration in pancreatic cancer was validated by functional enrichment analysis. ESTIMATE and single sample Gene Set Enrichment Analysis algorithms were used to further analyze immune infiltration of TTC22 in pancreatic cancer, and the results suggested that TTC22 inhibited tumor immunity and was negatively correlated with plasmacytoid dendritic cells. Reverse transcription-quantitative PCR further confirmed the differential expression of TTC22 in pancreatic cancer cell lines. Wound healing, Transwell and colony formation assays showed that TTC22 affected the migration and invasion of pancreatic cancer cells. These findings demonstrate that TTC22 may serve as a potential prognostic marker and therapeutic target for the management of pancreatic cancer.

SUBMITTER: Ding Y

PROVIDER: S-EPMC10688474 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition.

Ding Yuntao Y Wang Huizhi H Cao Wenyu W Cao Tianyu T Jiang Han H Yu Zhengyue Z Zhou Yujing Y Xu Min M

Oncology letters 20231110 1

The mortality rate of pancreatic adenocarcinoma is high, and the effect of traditional treatment is unsatisfactory, thus novel biomarkers are required. Although the important role of tetratricopeptide repeat domain 22 (TTC22) in colon cancer is well established, its precise role in pancreatic cancer remains unclear and requires further investigation. Pan-cancer analysis and single-cell sequencing revealed TTC22 was differentially expressed in various tumors, especially in pancreatic adenocarcino ...[more]

PMID: 38034483

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Project description:BACKGROUND:Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. METHODS:Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. RESULTS:A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. CONCLUSIONS:In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.

Dataset Information

TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition.

Publications

TTC22 as a potential prognostic marker and therapeutic target in pancreatic cancer: Insights into immune infiltration and epithelial‑mesenchymal transition.

Similar Datasets

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