{
  "abstract": "Background To investigate the impact of ITGBL1 on 5-fluorouracil (5-FU) sensitivity in colorectal cancer and explore its underlying molecular mechanisms.Methods ITGBL1 in CRC and adjacent normal tissues were compared using the GEPIA database. Kaplan-Meier survival analysis was performed to evaluate the association between ITGBL1 expression and patient prognosis. Immunohistochemistry (IHC) was used to analyze ITGBL1 protein expression in CRC and adjacent tissues. The correlation between ITGBL1 expression and clinicopathological characteristics was assessed. Cell proliferation and 5-FU sensitivity were evaluated using CCK-8 and colony formation assays. mRNA sequencing (mRNA-seq) was performed to identify differentially expressed genes between control and ITGBL1-knockdown cells. qRT-PCR was used to validate FBN1 expression in ITGBL1-knockdown cells. Furthermore, FBN1 was overexpressed in ITGBL1-knockdown cells using plasmids to investigate its effects on cell proliferation and 5-FU sensitivity.Results Analysis of the GEPIA database revealed that ITGBL1 mRNA was highly expressed in CRC tissues. Kaplan-Meier survival analysis indicated that high ITGBL1 expression was associated with poorer overall survival (log-rank P = 0.025). IHC results confirmed that ITGBL1 protein was significantly upregulated in CRC tissues ( IDDF2026-ABS-0288 Figure 1). ITGBL1 expression was significantly correlated with lymph node metastasis, distant metastasis, and clinical stage. In vitro experiments showed that ITGBL1 knockdown significantly inhibited the proliferation of HCT116 and RKO cells (IDDF2026-ABS-0288 Figure 2, IDDF2026-ABS-0288 Figure 3). Additionally, ITGBL1 knockdown reduced the IC50 value of 5-FU and enhanced the sensitivity of CRC cells to 5-FU (IDDF2026-ABS-0288 Figure 4). mRNA-seq analysis revealed that FBN1 was the most significantly downregulated gene in ITGBL1-knockdown cells. A moderate positive correlation was observed between ITGBL1 and FBN1 in the GEPIA database (IDDF2026-ABS-0288 Figure 5). qRT-PCR confirmed that FBN1 expression was decreased in ITGBL1-knockdown cells. Overexpression of FBN1 reversed the inhibitory effects of ITGBL1 knockdown on cell proliferation and 5-FU sensitivity (IDDF2026-ABS-0288 Figure 6).Conclusions ITGBL1 is highly expressed in CRC tissues, and its expression level is associated with lymph node metastasis, distant metastasis, TNM stage, and poor prognosis. ITGBL1 may regulate CRC cell proliferation and 5-FU sensitivity through FBN1, suggesting that ITGBL1 plays an important role in CRC progression and chemoresistance. It may serve as a potential therapeutic target and prognostic biomarker for CRC.Abstract IDDF2026-ABS-0288 Figure 1Abstract IDDF2026-ABS-0288 Figure 2Abstract IDDF2026-ABS-0288 Figure 3Abstract IDDF2026-ABS-0288 Figure 4Abstract IDDF2026-ABS-0288 Figure 5Abstract IDDF2026-ABS-0288 Figure 6",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, The First Affiliated Hospital of University, China"
      ],
      "name": "Zhijie Zheng"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The First Affiliated Hospital of University, China"
      ],
      "name": "Nan Gao"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The First Affiliated Hospital of University, China"
      ],
      "name": "Sihui Zou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The First Affiliated Hospital of University, China"
      ],
      "name": "Rui Li"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The First Affiliated Hospital of University, China"
      ],
      "name": "Weichang Chen"
    }
  ],
  "title": "IDDF2026-ABS-0288 ITGBL1 regulates FBN1-mediated 5-fluorouracil sensitivity in colorectal cancer",
  "uid": "28dd3b21-a57c-5131-b6c6-f4b77ef28727"
}