Background: Colorectal cancer (CRC) is a highly devastating cancer. Ca²⁺-dependent channels are now considered key regulators of tumor progression. In this study, we aimed to investigate the association of non-voltage gated Ca²⁺ channels and Ca²⁺-dependent potassium channels (KCa) with CRC using the transcriptional profile of their genes. Methods: We selected a total of 35 genes covering KCa channels KCNN1–4, KCNMA1 and their subunits KCNMB1–4, endoplasmic reticulum (ER) calcium sensors STIM1 and STIM2, Ca²⁺ channels ORAI1–3 and the family of cation channels TRP (TRPC1–7, TRPA1, TRPV1/2,4–6 and TRPM1–8). We analyzed their expression in two public CRC datasets from The Cancer Genome Atlas (TCGA) and GSE39582. Results: KCNN4 and TRPM2 were induced while KCNMA1 and TRPM6 were downregulated in tumor tissues comparing to normal tissues. In proximal tumors, STIM2 and KCNN2 were upregulated while ORAI2 and TRPM6 were downregulated. ORAI1 decreased in lymph node metastatic tumors. TRPC1 and ORAI3 predicted poor prognosis in CRC patients. Moreover, we found that ORAI3/ORAI1 ratio is increased in CRC progression and predicted poor prognosis. Conclusions: KCa and Ca²⁺ channels could be important contributors to CRC initiation and progression. Our results provide new insights on KCa and Ca²⁺ channels remodeling in CRC.

Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI.

Background: Patients with Lynch syndrome are at increased risk of gastric and duodenal cancer. Upper gastrointestinal endoscopy surveillance is generally proposed, even though little data are available on upper gastrointestinal endoscopy in these patients. The aim of this retrospective study was to evaluate the prevalence and incidence of gastrointestinal lesions following upper gastrointestinal endoscopy examination in Lynch patients. Methods: A large, multicentre cohort of 172 patients with a proven germline mutation in one of the mismatch repair genes and at least one documented upper gastrointestinal endoscopy screening was assessed. Detailed information was collected on upper gastrointestinal endoscopy findings and the outcome of endoscopic follow-up. Results: Seventy neoplastic gastrointestinal lesions were diagnosed in 45 patients (26%) out of the 172 patients included. The median age at diagnosis of upper gastrointestinal lesions was 54 years. The prevalence of cancer at initial upper gastrointestinal endoscopy was 5% and the prevalence of precancerous lesions was 12%. Upper gastrointestinal lesions were more frequent after 40 years of age (p < 0.001). Helicobacter pylori infection was associated with an increased prevalence of gastric, but not duodenal, lesions (p < 0.001). Conclusions: Neoplastic upper gastrointestinal lesions are frequent in patients with Lynch syndrome, especially in those over 40 years of age. The results of our study suggest that Lynch patients should be considered for upper gastrointestinal endoscopic and Helicobacter pylori screening.

Background & aim: Resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (CRC) is frequent and prognostic biomarkers are lacking. MicroRNAs (miR) are good candidates in this ...