Clinicopathological significance of intelectin-1 in colorectal cancer: Intelectin-1 participates in tumor suppression and favorable progress

Our plain-English summary of Clinicopathological significance of intelectin-1 in colorectal cancer: Intelectin-1 participates in tumor suppression and favorable progress, by N. Katsuya, K. Sentani, Y. Sekino, et al (Pathology International, 2020).

The study

• Authors: N. Katsuya, K. Sentani, Y. Sekino, Y. Yamamoto, G. Kobayashi, T. Babasaki, N. Oue, V.J. Amatya, Y. Takeshima, W. Yasui
• Journal: Pathology International
• Published: 2020;70(12):943-952
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Intelectin-1 (ITLN1) is an adipokine with an anti-inflammatory function that is involved in neoplastic diseases such as pleural mesothelioma and gastric and prostate cancers. However, the expression and function of ITLN1 in colorectal cancer (CRC) remain unknown. To identify novel prognostic markers or therapeutic targets for CRC, we focused on ITLN1 protein. By immunohistochemistry, 87 (59%) of 148 CRC cases showed reduced expression of ITLN1. ITLN1-reduced CRC cases were associated with higher M grades (P = 0.0017) than ITLN1-retained CRC cases. Furthermore, the cases with ITLN1 retained expression tended toward a more favorable prognosis than those with reduced expression. Cell growth of the CRC cell lines transfected with ITLN1 siRNA were greater than those of the negative control cell lines transfected with siRNA. Levels of phosphorylated epidermal growth factor receptor, Erk and Akt were higher in the CRC cells transfected with ITLN1 siRNA than in control cells. Immunohistochemical analysis of human colorectal polyp specimens also revealed a sequential decrease in the expression of ITLN1 through both the conventional adenoma-carcinoma pathway and the serrated pathway. These results indicated that ITLN1 might play an important role in regulating colorectal tumorigenesis.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

In plain English

This tissue and laboratory study from Hiroshima University, Japan, was about colorectal (bowel) cancer, not asbestos. Pleural mesothelioma is mentioned only as background from other research. The authors examined a protein called intelectin-1 (ITLN1) in tumors removed from 148 patients who had surgery between 1997 and 2009. Staining showed reduced ITLN1 in 87 (59%) of the 148 tumors. Reduced ITLN1 was more common in tumors that had spread to distant sites (17 of 19, versus 70 of 129 without distant spread), in more advanced stages, and in tumors with a higher budding grade. Patients with reduced ITLN1 had poorer survival (P = 0.0155), and in a multivariate analysis reduced ITLN1 was an independent predictor of survival. In two colorectal cancer cell lines, lowering ITLN1 increased cell growth and raised levels of activated growth-signaling proteins (EGFR, Erk and Akt). Among polyp specimens, low-grade adenomas showed more ITLN1 than high-grade adenomas. The authors concluded that ITLN1 may have potential as a predictive biomarker for survival in colorectal cancer. The article contains several inconsistent numbers, and its survival table was not included in the text.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of surgically removed tumor tissue (immunohistochemistry, with survival analysis), combined with cell-line laboratory experiments
• Who was studied: 148 patients (70 men, 78 women) with colorectal cancer who had curative surgery between 1997 and 2009 at Hiroshima University Hospital, Japan, with no preoperative radiotherapy or chemotherapy. Also 20 paired tumor and normal samples, 96 colorectal polyp specimens, and colorectal cancer cell lines (DLD-1 and WiDr among others).
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was the level of the protein ITLN1 in tumor tissue, and laboratory reduction of ITLN1 using siRNA in cell lines.
• Main results:
  • ITLN1 staining was reduced in 87 (59%) of the 148 colorectal cancer cases.
  • ITLN1 messenger RNA was reduced in 16 (80%) of 20 tumors compared with matching normal tissue.
  • Cases with reduced ITLN1 had more advanced M classification (P = 0.0017), tumor stage (P = 0.005) and budding grade (P = 0.001) than cases with preserved ITLN1. In the table, 17 (89%) of 19 M1 cases had reduced ITLN1, compared with 70 (54%) of 129 M0 cases.
  • Reduced ITLN1 was significantly associated with poorer prognosis in the 148 patients (P = 0.0155).
  • In multivariate analysis, reduced ITLN1, M grade and tumor stage were independent predictors of survival. Hazard ratios are in a supplementary table that is not in the text.
  • In DLD-1 cells, reducing ITLN1 with siRNA significantly increased cell viability compared with control cells. Similar results were obtained in WiDr cells.
  • Levels of phosphorylated EGFR, Erk and Akt were higher in DLD-1 and WiDr cells with reduced ITLN1 than in control cells.
  • Reduced ITLN1 occurred together with nuclear beta-catenin (P = 0.012) and with expression of several other cancer-related molecules (MMP7, CDX2, MUC5AC, claudin-18, CD44).
  • In 96 colorectal polyp specimens, low-grade conventional adenomas showed higher ITLN1 expression than high-grade conventional adenomas.
• The authors' conclusion: The authors concluded that reduced ITLN1 was independently associated with poor prognosis, and that ITLN1 may have potential as a predictive biomarker for survival in colorectal cancer.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Colorectal Cancer, Pleural Mesothelioma, Immunohistochemistry, Prognosis, Carcinoma, Carcinogenesis.

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