Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 13;25(1):582.
doi: 10.1186/s12876-025-04197-z.

Evaluation of PINK1 protein expression as a predictive marker for the efficacy of adjuvant chemotherapy in colorectal cancer: a retrospective study

Takatsugu Fujii  1 , Masataka Hirasaki  2 , Yasuo Kamakura  3 , Tomonori Kawasaki  4 , Satoshi Yamasaki  3 , Yasuhiro Ishiyama  1 , Chikashi Hiranuma  1 , Tetsuya Hamaguchi  3   5 , Yasumitsu Hirano  1 , Shinichi Sakuramoto  1
Affiliations

Evaluation of PINK1 protein expression as a predictive marker for the efficacy of adjuvant chemotherapy in colorectal cancer: a retrospective study

Takatsugu Fujii et al. BMC Gastroenterol. .

Abstract

Background: PTEN-induced kinase 1 (PINK1) is involved in mitochondrial quality control via mitophagy, and recent studies have reported that its overexpression is associated with chemoresistance and poor prognosis in multiple malignant tumors. However, the clinical significance of PINK1 expression in colorectal cancer remains unclear. In this study, we investigated the association among PINK1 protein expression, clinicopathological factors, and prognosis in patients with colorectal cancer who underwent adjuvant chemotherapy after curative surgery.

Methods: We retrospectively analyzed 83 patients with colorectal cancer who underwent curative surgery and fluoropyrimidine-based adjuvant chemotherapy in 2016. Expression of PINK1 and autophagy-related protein LC3 was evaluated by immunohistochemical staining, and the percentage of positive cells and staining intensity were scored. The association between PINK1 expression and the prognosis of 25 patients with confirmed recurrence was analyzed in detail. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards models. Furthermore, in 11 cases with RNA sequencing analysis available among the recurrent cases, gene expression profiles were compared based on PINK1 expression levels, and biological characteristics were evaluated.

Results: PINK1 high expression was observed in 42.2% of the cases. No significant association was found between PINK1 and LC3 expression and overall survival (OS) or recurrence-free survival (RFS). However, in the recurrence group (n = 25), PINK1 high expression was significantly associated with a shorter OS (p = 0.024). In multivariate analysis, histological differentiation grade and high PINK1 expression were identified as independent prognostic factors (PINK1: hazard ratio 5.345, 95% confidence interval, 1.343-21.276; p = 0.017). RNA sequencing revealed increased expression of genes associated with autophagy and amino acid transport in the high PINK1 expression group.

Conclusions: High PINK1 expression is associated with poor prognosis in colorectal cancer recurrence and may be involved in the promotion of chemotherapy resistance and cellular stress tolerance. PINK1 is a promising biomarker as a prognostic predictor and a new therapeutic target for adjuvant chemotherapy after surgery.

Keywords: Adjuvant chemotherapy; Autophagy; Chemoresistance; Colorectal cancer; LC3; PINK1; Single nucleotide polymorphism.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study adhered to the ethical standards of the Declaration of Helsinki and its subsequent amendments. This study was approved by the Institutional Review Board of the Saitama Medical University International Medical Center (2022 − 113 and 2024-055). The requirement for informed consent was waived by the Institutional Review Board of Saitama Medical University International Medical Center (2022 − 113 and 2024-055) in view of the retrospective nature of this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Pink1 and LC3 immunostaining in colorectal cancer.a–c Pink1 immunostained sections (with respect to intensity). d–f LC3 immunostained sections (with respect to intensity). Scale bar represents 100 μm. Magnification: ×200
Fig. 2
Fig. 2
Correlation between LC3 or PINK1 expression and prognosis in surgical specimens of colorectal cancer patients. Correlation between the expression of PINK1 (a, b) or LC3 (c, d) in surgical specimens before adjuvant chemotherapy and recurrence-free survival and overall survival in 82 patients with colorectal cancer who received postoperative adjuvant chemotherapy
Fig. 3
Fig. 3
Correlation between prognosis and expression of LC3 or PINK1 in surgical specimens from patients with recurrent colorectal cancer. Correlation between the expression of PINK1 (a) or LC3 (b) in surgical specimens before adjuvant chemotherapy and overall survival in 25 patients with colorectal cancer who had recurred after adjuvant chemotherapy
Fig. 4
Fig. 4
RNAseq analysis of CRCs with different expression levels of PINK1 protein. (a) Volcano plot of DEGs (fold change ≥ 2 and p ≤ 0.05) for PINK1 low CRC group (n = 7) and PINK1 high CRC group n = 4. (b) Summary of GO and KEGG analysis for DEG of PINK1 high CRC group. (c) Summary of GO and KEGG analysis of enriched genes in PINK1 high CRC group by GSEA analysis. (d) Part of GSEA plot enriched in PINK1 high CRC. NES, normalized enrichment score. (e) Heatmap of genes involved in “PIECEMEAL MICROAUTOPHAGY OF THE NUCLEUS” and “REGULATION OF AUTOPHAGY” enriched by GSEA. Red and blue represent high and low expression, respectively
See this image and copyright information in PMC

References

    1. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK et al. NCCN Guidelines Version 3.2021 Colon Cancer Continue NCCN Guidelines Panel Disclosures. 2021;19:329– 59. 10.6004/jnccn.2021.0012 - PubMed
    1. Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American society of clinical oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19. 10.1200/JCO.2004.05.063. - PubMed
    1. O’Connell MJ, Campbell ME, Goldberg RM, Grothey A, Seitz JF, Benedetti JK, et al. Survival following recurrence in stage II and III colon cancer: findings from the ACCENT data set. J Clin Oncol. 2008;26:2336–41. 10.1200/JCO.2007.15.8261. - PubMed
    1. Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091–7. 10.1056/NEJMOA010957. - PubMed
    1. André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109–16. 10.1200/JCO.2008.20.6771. - PubMed

MeSH terms