Vertical level of blood cell division cycle 42 predicts response and survival benefits to PD-1 inhibitor-based regimen in metastatic colorectal cancer patients

References

• Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA. 2021;325(7):669–685.
   PubMed Web of Science ®Google Scholar
• Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet. 2019;394(10207):1467–1480.
   PubMed Web of Science ®Google Scholar
• Modest DP, Pant S, Sartore-Bianchi A. Treatment sequencing in metastatic colorectal cancer. Eur J Cancer. 2019;109:70–83.
   PubMed Web of Science ®Google Scholar
• Sharma P, Siddiqui BA, Anandhan S, et al. The next decade of immune checkpoint therapy. Cancer Discov. 2021;11(4):838–857.
   PubMed Web of Science ®Google Scholar
• Le DT, Kim TW, Van Cutsem E, et al. Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 2020;38(1):11–19.
   PubMed Web of Science ®Google Scholar
• Kawazoe A, Kuboki Y, Shinozaki E, et al. Multicenter phase I/II trial of napabucasin and pembrolizumab in patients with metastatic colorectal cancer (EPOC1503/SCOOP trial). Clin Cancer Res. 2020;26(22):5887–5894.
   PubMed Web of Science ®Google Scholar
• Wang F, He MM, Yao YC, et al. Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis. Cell Rep Med. 2021;2(9):100383.
   PubMedGoogle Scholar
• Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–1191.
   PubMed Web of Science ®Google Scholar
• Andre T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207–2218.
   PubMed Web of Science ®Google Scholar
• Mosaddeghzadeh N, Ahmadian MR. The RHO family GTPases: mechanisms of regulation and signaling. Cells. 2021;10(7):1831.
   Google Scholar
• Yan S, Ren X, Yang J, et al. Exosomal miR-548c-5p regulates colorectal cancer cell growth and invasion through HIF1A/CDC42 axis. Onco Targets Ther. 2020;13:9875–9885.
   PubMed Web of Science ®Google Scholar
• Liu M, Lang N, Qiu M, et al. miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells. Int J Cancer. 2011;128(6):1269–1279.
   PubMed Web of Science ®Google Scholar
• Gao L, Bai L, Nan Q. Activation of RHO GTPase Cdc42 promotes adhesion and invasion in colorectal cancer cells. Med Sci Monit Basic Res. 2013;19:201–207.
   PubMedGoogle Scholar
• Marques CA, Hahnel PS, Wolfel C, et al. An immune escape screen reveals Cdc42 as regulator of cancer susceptibility to lymphocyte-mediated tumor suppression. Blood. 2008;111(3):1413–1419.
   PubMed Web of Science ®Google Scholar
• Wurzer H, Filali L, Hoffmann C, et al. Intrinsic resistance of chronic lymphocytic leukemia cells to NK cell-mediated lysis can be overcome in vitro by pharmacological inhibition of Cdc42-Induced actin cytoskeleton remodeling. Front Immunol. 2021;12:619069.
   PubMed Web of Science ®Google Scholar
• Nakayama G, Ishigure K, Yokoyama H, et al. The efficacy and safety of CapeOX plus bevacizumab therapy followed by capecitabine plus bevacizumab maintenance therapy in patients with metastatic colorectal cancer: a multi-center, single-arm, phase II study (CCOG-0902). BMC Cancer. 2017;17(1):243.
   PubMed Web of Science ®Google Scholar
• Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22(2):229–237.
   PubMed Web of Science ®Google Scholar
• Sun N, Ye L, Chang T, et al. microRNA-195-Cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7(10):6871–6879.
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–408.
   PubMed Web of Science ®Google Scholar
• Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–247.
   PubMed Web of Science ®Google Scholar
• Gao S, Xue J, Wu X, et al. The relation of blood cell division control protein 42 level with disease risk, comorbidity, tumor features/markers, and prognosis in colorectal cancer patients. J Clin Lab Anal. 2022;36(7):e24572.
   PubMed Web of Science ®Google Scholar
• Li G, Wang Y, Guo XB, et al. CDC42 regulates cell proliferation and apoptosis in bladder cancer via the IQGAP3-mediated ras/ERK pathway. Biochem Genet. 2022;60(6):2383–2398.
   PubMed Web of Science ®Google Scholar
• Huang D, Qiu H, Miao L, et al. Cdc42 promotes thyroid cancer cell proliferation and migration and tumor-associated macrophage polarization through the PTEN/AKT pathway. J Biochem Mol Toxicol. 2022;36(8):e23115.
   PubMed Web of Science ®Google Scholar
• Hu Z, Zhu J, Ma Y, et al. CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-kappaB signaling pathway promotes invasion and metastasis of CRC. Mol Ther Oncolytics. 2022;24:873–886.
   PubMed Web of Science ®Google Scholar
• Yaghoubi N, Soltani A, Ghazvini K, et al. PD-1/PD-L1 blockade as a novel treatment for colorectal cancer. Biomed Pharmacother. 2019;110:312–318.
   PubMed Web of Science ®Google Scholar
• Patel MR, Falchook GS, Hamada K, et al. A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer. Cancer Med. 2021;10(4):1183–1190.
   PubMed Web of Science ®Google Scholar
• Zhou H, Wang Y, Lin Y, et al. Preliminary efficacy and safety of camrelizumab in combination with XELOX plus bevacizumab or regorafenib in patients with metastatic colorectal cancer: a retrospective study. Front Oncol. 2021;11:774445.
   PubMed Web of Science ®Google Scholar
• Wu X, Lan X, Hu W, et al. CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer. Cancer Immunol Immunother. 2021;70(11):3235–3248.
   PubMed Web of Science ®Google Scholar
• Bortolomeazzi M, Keddar MR, Montorsi L, et al. Immunogenomics of colorectal cancer response to checkpoint blockade: analysis of the KEYNOTE 177 trial and validation cohorts. Gastroenterology. 2021;161(4):1179–1193.
   PubMed Web of Science ®Google Scholar
• Schrock AB, Ouyang C, Sandhu J, et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann Oncol. 2019;30(7):1096–1103.
   PubMed Web of Science ®Google Scholar
• Lei X, Lei Y, Li JK, et al. Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy. Cancer Lett. 2020;470:126–133.
   PubMed Web of Science ®Google Scholar