hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract

Abstract

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract.

Potassium channels: Novel targets for tumor diagnosis and chemoresistance

“…High expression of genes encoding Kv11.1 channels is associated with favorable prognosis in estrogen receptor-negative breast cancer ( 75 ). Extensive expression of Kv11.1 channels in gastrointestinal tumors may serve as an early diagnostic marker ( 76 ). Expression of KCNN4 is associated with disease-free survival, immune infiltration, and several other clinicopathological features and can serve as a diagnostic and prognostic biomarker in TC ( 86 ).…”

“…High Kv11.1 expression is associated with a favorable prognosis in estrogen receptor-negative breast cancer, and NS1643, a Kv11.1 activator, reduces the metastatic spread of breast tumors in vivo by inhibiting cell motility via β-catenin ( 75 ). Researchers have found that Kv11.1 is highly expressed in precancerous lesions of the gastrointestinal tract, and Kv11.1 can be used as an early diagnostic marker for gastrointestinal tumors ( 76 ). In addition, Kv11.1 is widely expressed in metastatic CRC, and combined treatment with Kv11.1 blockers and bevacizumab inhibits local tumor growth and metastatic spread ( 77 ).…”

The role of potassium channels in tumours of the gastrointestinal tract: a focus on the human ether‐à‐go‐go related gene 1 channels

“…In the colon–rectum, hERG1 is not expressed in healthy colonic mucosa and sigma diverticulitis (Dolderer et al., 2010; Lastraioli et al., 2004). Precancerous colon rectal adenoma lesions express the channel, although expression levels increase in high‐grade dysplastic colon rectal adenomas (Lastraioli et al., 2022). On the other hand, both the KCNH2 transcript and the hERG1 protein are highly expressed in CRC cell lines and primary samples (Lastraioli et al., 2004).…”