Objective: Colorectal cancer (CRC) is a commonly diagnosed human malignancy worldwide. Both epithelial-mesenchymal transition (EMT) and N6methyladenosine (m6A) modification play a crucial role in CRC development.This study aimed to construct a prognostic signature based on the genes related to EMT and m6A modification.Method: Firstly, the mRNA expression profiling of CRC tissues was analyzed using TCGA and GEO databases. The prognostic hub genes related to EMT and m6A modification were selected using weighted correlation network and cox regression analysis. The prognostic signature was constructed based on hub genes, followed by validation in three external cohorts. Finally, the expression of the representative hub gene was detected in clinical samples, and its biological role was investigated using assays in vivo and in vitro.Results: A prognostic signature was constructed using the following genes: YAP1, FAM3C, NUBPL, GLO1, JARID2, NFKB1, CDKN1B, HOOK1, and GIPC2. The signature effectively stratified the clinical outcome of CRC patients in the training cohort and two validation cohorts. The subgroup analysis demonstrated the signature could identify high-risk population from CRC patients within stage I-II or III-IV, female, male and elder patients. The signature was correlated with the infiltration of some immune cells (such as macrophage and regulatory T cells) and gene mutation counts. Finally, the hub gene GIPC2 was found to be downregulated in CRC tissues and most CRC cells lines. GIPC2 overexpression inhibited the malignant characteristics of CRC cells in vitro and in vivo through upregulating E-cadherin and downregulating N-cadherin, Vimentin, and Snail, while the opposite results were observed for GIPC2 knockdown in CRC cells.

BackgroundPrognostic nutritional index (PNI) has been identified as a reliable prognostic factor for cancer adjuvant therapy. However, its prognostic value in lung cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconclusive.MethodA systematic literature review and meta-analysis was performed based on online databases before March 1th 2023. The correlation of PNI with overall survival (OS) or progression-free survival (PFS) was determined using the hazard ratios (HRs) coupled with 95% confidence intervals (CIs). Then, a retrospective cohort enrolling 123 ICI-treated lung cancer patients from two hospitals was utilized for validation and further investigation.ResultsA total of 14 studies enrolling 1,260 lung cancer patients were included in the meta-analysis. The high PNI level was significantly correlated with better OS (HR = 2.56, 95% CI = 1.86–3.54) and PFS (HR = 1.91, 95% CI = 1.53–2.40) of the lung cancer patients. The subgroup analysis confirmed the results except for the PFS in patients receiving anti-PD-1 therapy (HR = 1.51, 95% CI = 0.86–2.65). In the retrospective study, the high PNI level was identified as a favorable factor for OS and PFS not only in the whole cohort but also in the subgroups stratified by non-small cell lung cancer and small cell lung cancer. The high PNI was also correlated with better anti-cancer therapy response and performed better than body mass index and serum albumin level in OS prediction. Finally, we established a novel prognostic nomogram based on PNI and other clinical parameters. The nomogram was found to perform well in predicting the 1-year OS of ICI-treated lung cancer patients.ConclusionBoth the meta-analysis and retrospective work demonstrate the PNI is a reliable prognostic factor for advanced lung cancer patients receiving ICI-based therapies. Our study further highlights the crucial role of nutrition assessment and intervention in cancer immunotherapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023424146.

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