Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

Lildballe, Dorte Launholt; Nguyen, Kimsa; Poulsen, Steen Seier; Nielsen, Henning Overgaard; Nexø, Ebba

doi:10.1016/j.ejso.2010.11.001

Cited by 34 publications

(21 citation statements)

References 28 publications

(13 reference statements)

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“…In addition, upregulation of TCN1 both in plasm and tumor tissue have been reported in a number of solid neoplasms including HCC, salivary gland tumors, cancers of the breast, kidney, lung and stomach, and endocervical adenocarcinoma 15, 17-24, 41. Previous studies have suggested that increased serum level and expression of TCN1 in patients with HCC or secondary liver metastasis might be due to a diminished clearance of TCN1 in the liver 38, 42. On the other hand, overexpression of TCN1 in other solid malignancies has been inferred mainly to be an excess synthesis of its production by tumor cells themselves or to an increase of hypergranulocytosis 17, 36, 38.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Lee¹,

Wei²,

Tian³

et al. 2017

J. Cancer

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Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT.Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS).Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison.Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Lee¹,

Wei²,

Tian³

et al. 2017

J. Cancer

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“…The underlying pathogenesis leading to high Cbl levels is poorly elucidated, with a few exceptions (6,10,11). It is not thought to involve increased Cbl intake because intestinal absorption capacity is saturable (31) and high physiological consumption does not increase plasma Cbl levels substantially.…”

Section: Discussionmentioning

confidence: 99%

“…On one hand, a high prevalence of elevated Cbl levels has been reported in patients with liver cancer (6,7), other solid tumors (8,9), and hematological malignancies (10,11). On the other hand, some studies have indicated a high prevalence of cancer, both hematological and solid tumors, among patients with high Cbl levels (3,5).…”

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confidence: 99%

Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study

Arendt

Pedersen

Nexø

et al. 2013

JNCI: Journal of the National Cancer Institute

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BackgroundA substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined.MethodsWe conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population. Data on cancer incidence (follow-up 1998–2010), Cbl treatment, and prior diagnoses were obtained from medical registries. Patients receiving Cbl treatment were excluded. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided.ResultsWe identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk increased with higher Cbl levels and was highest during the first year of follow-up (Cbl 601–800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88; both P < .001). The risks were particularly elevated for hematological and smoking- and alcohol-related cancers for persons with high Cbl levels.ConclusionsHigh Cbl levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high Cbl levels.

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“…Other serum findings in patients with FLC include elevated transcobalamin I levels [7, 37, 38], transcobalamin 2 [7], and vitamin B12 binding capacity [7, 19, 23, 37, 39, 40]. Transcobalamin I is also known as haptocorrin and is a glycoprotein that in normal physiology is made largely in the salivary glands, from where it is secreted into the digestive tract and protects vitamin B12 (also known as cobalamin) from degradation in the stomach.…”

Section: Clinical Findingsmentioning

confidence: 99%

Fibrolamellar Carcinoma: 2012 Update

Torbenson

2012

Scientifica

146

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Fibrolamellar carcinomas are a unique type of primary liver cancer. They occur most commonly in children and young adults. Their etiology remains a mystery, as they are not associated with chronic liver disease. Fibrolamellar carcinomas are not indolent tumors, but have an overall better prognosis than typical hepatocellular carcinomas, in part because of the younger age at presentation and the lack of cirrhosis. The most important prognostic feature is whether the tumor is resectable. Histologically, the tumor is made up of large cells that contain abundant mitochondria. The nuclei of the tumor cells have prominent nucleoli. The tumor cells induce the formation of extensive intratumoral fibrosis, which often grows in parallel, or lamellar bands. The tumor cells clearly show hepatocellular features but are also unique in showing both biliary and neuroendocrine differentiation. The uniqueness of fibrolamellar carcinoma extends to their molecular findings. While the genetic abnormalities that lead to fibrolamellar carcinomas are not yet known, studies have shown that they lack mutations in the genes most commonly mutated in typical hepatocellular carcinoma (TP53 and CTNNB1). In this paper, the clinical, pathological, and basic science literature on fibrolamellar carcinoma is comprehensively reviewed. Key areas of needed research are also discussed.

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Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

Cited by 34 publications

References 28 publications

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study

Fibrolamellar Carcinoma: 2012 Update

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