KK-LC-1 is a CTA due to its absence of expression in normal tissues, except for the testis. However, it is expressed in cancers of multiple organs [7, 10]. Furthermore, in an earlier study, Fukuyama et al. clarified the specific phenomena at the basis of the correlation between KK-LC-1 expression and Hp infection. Additionally, we previously showed how KK-LC-1 expression was frequently detected at non-tumour sites of the stomach occurring GC [14, 16]. However, from these studies, it remained unclear whether KK-LC-1 was expressed in the stomach of patients who were not carrying a tumour and with Hp infection. In the present study, we proved that KK-LC-1 was frequently expressed in non-tumour sites of the GC stomach but infrequently in those of non-GC stomach (Fig. 1). Furthermore, we also proved that, while KK-LC-1 expression is correlated with Hp infection, it is not exclusively an indicator of Hp infection.
KK-LC-1’s expression might become a new indicator for measuring precancerous levels in the stomach. The difference of non-tumour site between GC and non-GC is the precancerous level. Of note, epigenetic alterations were known as precancerous level indicators. In an earlier study, Compare et al. reported that global hypomethylation of the gastric mucosa gradually advanced from Hp-negative gastritis to Hp-positive gastritis, Hp-positive chronic gastritis and gastric carcinoma . In contrast, Leodolter et al. showed that global hypomethylation occurred during the early stages of gastritis, regardless of Hp infection . KK-LC-1’s expression may help us understand whether the stomach is close to a malignant level, independently from the accumulation of genetic/epigenetic alterations.
KK-LC-1 was not detected at non-tumour sites of the stomachs of three GC patients. However, its expression was detected in tumour sites of the same patients. Such an issue may be resolved by sampling multiple mucosa sites from the lower corpus. Supplementary Figure S1 and results from our previous study show that KK-LC-1's expression rate in the lower corpus was of 68.1 and 66.1%, respectively .
We observed one non-GC patient whose non-tumour sites of the stomach expressed KK-LC-1; this patient was later diagnosed with GC. Specifically, following a first pathological observation of a biopsy, an adenoma was identified. However, the sympatric specimen of endoscopic submucosal dissection (ESD) has a diagnosis of adenocarcinoma in adenoma. On the biopsy, RUT was performed and its specimen, allopatric of ESD, expressed KK-LC-1. This phenomenon may indicate that detecting KK-LC-1 marks GC’s presence in the stomach’s allopatric sites.
Additionally, KK-LC-1 expression was observed in non-tumour sites of GC patients. Of note, GC patients undergoing mucosal resection (including ESD) more frequently presented with metachronous cancers from gastric remnants than during surgical resection. Such findings suggest that KK-LC-1 might represent a prediction marker of GC occurrence. Non-GC patients, in whom KK-LC-1 was detected, are under follow-up to identify possible GC development. However, all non-GC patients with KK-LC-1 received antibiotics against Hp. Therefore, genetic/epigenetic alterations caused by Hp will not accumulate, preventing GC from developing. Nonetheless, GC can occur following Hp eradication . In the event that, in the future, GC occurs in the seven non-GC patients with KK-LC-1, the latter might become a new predictive marker for GC.