EREG silencing inhibits tumorigenesis via inactivating ERK/p38 MAPK pathway in pancreatic ductal adenocarcinoma.

Epiregulin (EREG) is a member of the epidermal growth factor (EGF) family. An increasing body of evidence has demonstrated the pivotal role of EREG in the pathogenesis and progression of various malignancies. However, the clinical significance and biological role of EREG in pancreatic ductal adenocarcinoma (PDAC) have yet to be fully elucidated. We found that EREG is highly expressed in PDAC tissues compared with paracancerous tissues through public databases and clinical samples. High EREG expression predicted worse overall survival (OS) and recurrence-free survival (RFS) in patients with PDAC. Multivariate analysis revealed that EREG can serve as an independent prognostic indicator. In addition, EREG silencing inhibited PDAC cell proliferation, migration, progression, altered cell cycle, facilitated apoptosis in vitro and suppressed tumor growth in vivo. Conversely, EREG overexpression facilitated the proliferation, migration, and invasion in PaTu-8988 t cell. Through transcriptome sequencing and experimental verification, we found EREG mediates PDAC tumorigenesis through ERK/p38 MAPK signaling pathway. Moreover, we found EREG expression is closely related to PD-L1 expression in PDAC tissues and cells. Therefore, EREG is expected to be a prospective prognostic and therapeutic marker for PDAC.

Clinical efficacy and safety evaluation of camrelizumab plus lenvatinib in adjuvant therapy after hepatocellular carcinoma surgery.

Objective: To assess the efficacy and safety of camrelizumab plus different targeted drugs in adjuvant therapy after hepatocellular carcinoma (HCC) surgery. Patients and methods: This retrospective cohort study included HCC patients who, after undergoing failed postoperative adjuvant lenvatinib therapy, received intravenous camrelizumab 200 mg every 3 weeks (C group, n = 97), camrelizumab plus oral apatinib 250 mg daily (C+A group, n = 125), camrelizumab plus oral lenvatinib 12 mg daily (for bodyweight ≥60 kg)/lenvatinib 8 mg daily (for bodyweight <60 kg) (C+L group, n = 120), or camrelizumab plus oral sorafenib 400 mg bi-daily (C+S group, n = 114) between October 2020 and October 2021. The outcomes including the objective response rate (ORR) and disease control rate (DCR) were evaluated by RECIST 1.1 and iRECIST. The median progression-free survival (mPFS), median overall survival (mOS), 6-month OS rate, 12-month OS rate, and adverse events were evaluated. Results: As of 31 May 2022 with last follow-up time, the ORR was 17.2% for the C group, 44.6% for the C+A group, 47.9% for the C+L group, and 36.3% for the C+S group. The DCR was 72.0% for the C group, 81.8% for the C+A group, 85.5% for the C+L group, and 77.9% for the C+S group. The mPFS was 11.0 months (10.1-12.8) for the C group, 14.0 months (12.7-16.5) for the C+A group, 18.0 months (16.9-20.1) for the C+L group, and 12.0 months (9.7-14.4) for the C+S group. The mOS was 13.0 months (11.6-15.3) for the C group, 17.0 months (15.8-19.4) for the C+A group, 19.0 months (17.7-20.2) for the C+L group, and 15.0 months (14.1-17.3) for the C+S group. Grade 3 or 4 treatment-related adverse events occurred in 14 patients (14.4%) for the C group, 10 patients (8.0%) for the C+A group, 5 patients (4.2%) for the C+L group, and 11 patients (9.6%) for the C+S group. The most common adverse events were fatigue and transaminitis. Conclusion: Camrelizumab combined with lenvatinib as adjuvant therapy showed promising efficacy and manageable safety in HCC patients. It might be a potential adjuvant therapy or second-line treatment for these patients.