High level of circulating vitamin D during neoadjuvant therapy may lower risk of metastatic progression in high-risk rectal cancer

Abrahamsson, Hanna; Porojnicu, Alina Carmen; Lindstrøm, Jonas Christoffer; Dueland, Svein; Flatmark, Kjersti; Hole, Knut Håkon; Seierstad, Therese; Moan, Johan; Redalen, Kathrine Røe; Meltzer, Sebastian; Ree, Anne Hansen

doi:10.1186/s12885-019-5724-z

Cited by 14 publications

(23 citation statements)

References 43 publications

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“…The highly similar effect of calcitriol on colon tumor and rectal tumor organoids is consistent with the finding that colon and rectal cancers, excluding hypermutated cancers, have similar patterns of genetic alterations [ 65 ]. Moreover, our finding also agrees with the proposed protective effect of vitamin D on both colon and rectal cancers [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Discussionsupporting

confidence: 92%

“…The gut physiology is profoundly affected by the action of vitamin D [ 17 ], and observational studies have established a link between vitamin D deficiency and an elevated risk and poor prognosis of CRC, suggesting that colon and rectal cancer patients might preferentially benefit from an adequate vitamin D status [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Data from recent interventional clinical studies indicate that the addition of vitamin D to standard chemotherapy improves the progression-free survival of metastatic CRC patients [ 29 ]; however, another randomized trial showed no preventive effect on adenoma recurrence [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Costales-Carrera

Fernández‐Barral

Bustamante-Madrid

et al. 2020

Cancers

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Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Costales-Carrera

Fernández‐Barral

Bustamante-Madrid

et al. 2020

Cancers

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“…The antitumour effect of vitamin D is a popular research topic. Epidemiological studies have compared the relationship between serum vitamin D levels and prognosis in patients with breast cancer 25 and rectal cancer 26 and have found that the higher the serum level of vitamin D is, the better is patient prognosis. The regulatory relationship between vitamin D and tumours has not yet been elucidated, and its mechanism has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Huang

Zhang

et al. 2019

Cell Death Dis

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Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.

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“…In recent years, there has been an increasing number of studies investigating the effect of 25-OH vitamin D on progression-free survival and overall survival in patients with colorectal cancer (24)(25)(26). It has been also revealed that infective complications are increased in hospitalized patients with vitamin D de ciency because of its decreased immunomodulatory effects (27,28).…”

Section: Discussionmentioning

confidence: 99%

The relation of preoperative 25-OH Vitamin D Levels with Postoperative Complications in Patients undergoing Colorectal Cancer Surgery

Balci

Çetindağ

Kılınç

et al. 2020

Preprint

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Background: To investigate the effect of preoperative 25-OH vitamin D levels on postoperative complications in patients undergoing colorectal cancer surgery.Methods: Consecutive newly diagnosed colorectal cancer patients who met the inclusion criteria were prospectively included in this single-center observational study. Preoperative 25-OH vitamin D levels were measured and analyzed for association with postoperative complications using univariable and multivariable logistic regression analyses.Results: A total of 104 colorectal cancer patients were included in this study. Preoperative 25-OH vitamin D levels were found to be <10 ng/ml in 31 (29.8%) patients, 10-20 ng/ml in 42 (40.4%) patients, between 20-30 ng/ml in 25 (24%) patients and >30 ng/ml in 6 (5.8%) patients. In patients with infective complications, the mean value of 25-OH vitamin D levels were 12.33 (±6.306) ng/ml which was found to be statistically significant (p:0.026). In univariable logistic regression analyses, variables found to be associated with postoperative complications were age ≥ 65, male gender and preoperative 25-OH vitamin D levels, whereas in multivariable analyses, preoperative levels of 25-OH vitamin D were not found to be related with postoperative complications.Conclusions: We demonstrated that vitamin D deficiency is a significant risk factor for development of infective complications and seems to be independently associated with postoperative complications in patients undergoing colorectal cancer surgery.

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High level of circulating vitamin D during neoadjuvant therapy may lower risk of metastatic progression in high-risk rectal cancer

Cited by 14 publications

References 43 publications

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

The relation of preoperative 25-OH Vitamin D Levels with Postoperative Complications in Patients undergoing Colorectal Cancer Surgery

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