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Background It is unclear whether the long non-coding RNA (lncRNA) OTX2 antisense RNA 1 (OTX2-AS1) plays a pivotal role in gastric cancer (GC). An analysis of The Cancer Genome Atlas (TCGA) database data and bioinformatics was used to explore the relationship between OTX2-AS1 and GC in the current study. Methods We evaluated the relationship between clinical features and OTX2-AS1 expression, prognostic factors, and the significant involvement of OTX2-AS1 in function using various statistical methods, such as Kaplan–Meier method, Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. GC cell lines were tested for OTX2-AS1 expression using qRT-PCR. Results A high level of OTX2-AS1 expression was significantly and negatively associated with Helicobacter pylori ( H pylori) infection in GC patients ( P = .006) and predicted a poorer overall survival (OS) (HR: 1.54; 95% CI: 1.10-2.14; P = .011), progression-free interval (PFI) (HR: 1.75; 95% CI: 1.22-2.51; P = .002) and disease-specific survival (DSS) (HR: 1.85; 95% CI: 1.21-2.85; P = .005) in GC patients. There was an independent correlation between OTX2-AS1 expression (HR: 1.771; 95% CI: 1.164-2.696; P = .008) and OS in patients with GC. There were differential enrichments for the OTX2-AS1 high expression phenotype in the olfactory transduction, G alpha (s) signaling events, keratinization, olfactory signaling pathway, and preimplantation embryo. OTX2-AS1 expression may be related to certain immune-infiltrating cells. Compared to gastric epithelial cells (GES-1), GC cell lines showed a significant increase in OTX2-AS1 expression. Conclusion There was a significant association between OTX2-AS1 expression in GC patients and poor survival, suggesting that it may be a useful biomarker for prognosis and immunotherapy outcome of stomach adenocarcinoma (STAD) in GC.

Most advanced colorectal cancer patients with proficient DNA mismatch repair or microsatellite stability (MSS) are insensitive to immune checkpoint inhibitor therapy. This report describes a heavily pretreated refractory colon adenocarcinoma patient with MSS. After experiencing four lines of treatment, the patient received the fifth-line therapy with the combined sintilimab, bevacizumab and chemotherapy. She achieved a long-term clinical outcome. The patient's progression-free survival after the fifth-line therapy was approximately 9.3 months, and her overall survival was approximately 57 months. To the best of our knowledge, this case represents the first report of durable clinical benefit from combination of an immune checkpoint inhibitor, bevacizumab and chemotherapy in a heavily pretreated patient with refractory metastatic colon adenocarcinoma with MSS.

Background: Unlike patients with advanced colorectal cancer (CRC) with deficient DNA mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors, most patients with advanced CRC with proficient DNA mismatch repair or microsatellite-stability (pMMR/MSS) tumors are not sensitive to immune checkpoint inhibitor (ICI) therapy. The current challenge is to find out innovative therapeutic combinations with ICIs for such patients. Case Presentation: In this study, we report a case of heavily pretreated refractory colon cancer with MSS but high-tumor mutation burden (TMB-H) tumors. After experiencing five lines of therapy, including chemotherapy and targeted therapy with anti-angiogenic inhibitor as well as anti-EGFR antibody, she received sixth-line therapy with combination of Sintilimab, Bevacizumab and chemotherapy, and obtained a durable clinical benefit. The patient’s progression-free survival (PFS) of sixth line therapy was about 9 months and overall survival (OS) has been over 4.6 years. Conclusion: To the best of our knowledge, this study represented the longest PFS of response to combination of ICI with other agents with different mechanisms of action in a heavily pretreated refractory colon cancer patient with MSS. Citation Format: Zhi Cui, Qi Wang, Muhong Deng, Erhong Meng, Sheng Liu, Quanli Han. Case report: long-term response to combination of Sintilimab, Bevacizumab and chemotherapy in a heavily pretreated refractory colon cancer patient with microsatellite stability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5190.