Blood Markers for Early Detection of Colorectal Cancer: A Systematic Review

Hundt, Sabrina; Haug, Ulrike; Brenner, Hermann

doi:10.1158/1055-9965.epi-06-0994

Cited by 192 publications

(144 citation statements)

References 105 publications

(101 reference statements)

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“…However, due to its limited sensitivity especially for early stage cancer, and its limited organ specificity, CEA is not regarded as suited as an individual diagnostic marker despite its undisputed value for monitoring tumor recurrence (35,36) and metastasis (37,38). In our analyses, CEA was found to have higher plasma levels in colorectal cancer patients at advanced stages compared with early ones, which is consistent with previous evidence (39). Nevertheless, although CEA is limited by its poor diagnostic efficacy as a single biomarker, it could still be used in a multimarker panel to enhance the diagnostic performance, which was also seen in other studies (40,41).…”

Section: Discussionsupporting

confidence: 83%

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

Chen

Zucknick

Werner

et al. 2015

Clinical Cancer Research

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Purpose: Novel noninvasive blood-based screening tests are strongly desirable for early detection of colorectal cancer. We aimed to conduct a head-to-head comparison of the diagnostic performance of 92 plasma-based tumor-associated protein biomarkers for early detection of colorectal cancer in a true screening setting.Experimental Design: Among all available 35 carriers of colorectal cancer and a representative sample of 54 men and women free of colorectal neoplasms recruited in a cohort of screening colonoscopy participants in 2005-2012 (N ¼ 5,516), the plasma levels of 92 protein biomarkers were measured. ROC analyses were conducted to evaluate the diagnostic performance. A multimarker algorithm was developed through the Lasso logistic regression model and validated in an independent validation set. The .632þ bootstrap method was used to adjust for the potential overestimation of diagnostic performance.Results: Seventeen protein markers were identified to show statistically significant differences in plasma levels between colorectal cancer cases and controls. The adjusted area under the ROC curves (AUC) of these 17 individual markers ranged from 0.55 to 0.70. An eight-marker classifier was constructed that increased the adjusted AUC to 0.77 [95% confidence interval (CI), 0.59-0.91]. When validating this algorithm in an independent validation set, the AUC was 0.76 (95% CI, 0.65-0.85), and sensitivities at cutoff levels yielding 80% and 90% specificities were 65% (95% CI, 41-80%) and 44% (95% CI, 24-72%), respectively.Conclusions: The identified profile of protein biomarkers could contribute to the development of a powerful multimarker blood-based test for early detection of colorectal cancer.

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Section: Discussionsupporting

confidence: 83%

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

Chen

Zucknick

Werner

et al. 2015

Clinical Cancer Research

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“…The prognosis of crc patients remains poor, with a 5-year survival rate of ~45% reported in most studies, despite significant improvements in early diagnosis, surgery, chemotherapy and radiotherapy (2). although TnM (tumor-node-metastasis) stage has been accepted as the most significant and independent prognostic factor, there are still many patients at the same stage who have different clinical outcomes (3). Therefore, the investigation and application of molecular markers responsible for the development and progression of crc are of utmost importance.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of HSP27 expression in colorectal cancer

et al. 2010

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Abstract. The heat shock protein 27-kda (HSP27) has been found overexpressed in several types of human cancer and is associated with treatment resistance and poor prognosis. Recent proteomic studies demonstrate that HSP27 is significantly overexpressed in colorectal cancer (crc). However, the relationship between HSP27 expression and patient prognosis remains nascent. in the present study, we aimed to investigate the expression of HSP27 and its correlation with clinicopathological parameters in crc patients. dysregulated expression of HSP27 was observed in neoplastic lesions, and appears to be involved in disease progression. immunohistochemical analysis showed that detectable HSP27 expression was found in 145/182 (79.7%) CRC cases. There was a significant correlation between HSP27 expression and TnM stage (P=0.003). Patients with low HSP27 expression had better survival than those with high HSP27 expression. additionally, multivariate analysis indicated that HSP27 expression is an independent prognostic marker for crc. These results suggest that elevated expression of HSP27 protein is a frequent event during the progression of crc. HSP27 might be used as a valuable prognostic marker for patients with crc. Introductioncolorectal cancer (crc) is one of the leading causes of malignancy-related deaths worldwide (1). The prognosis of crc patients remains poor, with a 5-year survival rate of ~45% reported in most studies, despite significant improvements in early diagnosis, surgery, chemotherapy and radiotherapy (2). although TnM (tumor-node-metastasis) stage has been accepted as the most significant and independent prognostic factor, there are still many patients at the same stage who have different clinical outcomes (3). Therefore, the investigation and application of molecular markers responsible for the development and progression of crc are of utmost importance.Heat shock proteins (HSPs) are detectable in virtually all organisms, from prokaryotes to mammals, and play a fundamental role in the maintenance of cellular homeostasis (4). under physiological conditions, HSPs are constitutively expressed at a low level and function as molecular chaperones that fulfill important roles for protein folding, cellular signaling and protein degradation (5). HSPs have a stimulated synthesis in response to a variety of stressful stimuli (e.g., heat, heavy metal, infection or inflammation) and promote the refolding of damaged proteins (6). HSPs are classified by their molecular weight; the main HSP families comprise HSP110, HSP90, HSP70, HSP60 and the small HSPs (7).HSP27, a small HSP, is ubiquitously expressed at low levels in normal cells (8). in contrast, its aberrant expression has been reported in a variety of human cancers, including breast (9), ovarian (10), gastric (11), prostate (12), endometrial (13), liver (14), bladder (15) and leukemia (16). Furthermore, elevated HSP27 levels in breast, ovarian, gastric, and prostate cancer is associated with aggressive growth and resistance to chemotherapy or radiotherapy, and hen...

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“…Both publications identify the current absence of largescale validation research as a major barrier to future progress in the development of new biomarkers for cancer risk assessment and early detection (1,2). An example of the difficulties encountered in early-phase validation research using high-throughput protein detection technology is provided in the publication of Parekh et al (3) in this issue of Cancer Epidemiology, Biomarkers & Prevention.…”

Section: The Validation Conundrummentioning

confidence: 99%

“…As called for by both reviews in this issue (1,2), the resources required to complete the validation of biomarkers are beyond the capabilities of individual laboratories, investigators, or institutions. Collaborative research groups that are vertically integrated with basic, population, and clinical scientists, such as the National Cancer Institute -sponsored Early Detection Research Network, can offer the necessary resources to successfully validate promising biomarkers that may reduce cancer mortality.…”

Section: Practical Considerations Of Biomarker Validationmentioning

confidence: 99%

Biomarkers for Cancer Risk, Early Detection, and Prognosis: The Validation Conundrum

Brenner

Normolle

2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Blood Markers for Early Detection of Colorectal Cancer: A Systematic Review

Abstract: Larger prospective studies using study populations representing a screening population are needed to verify promising results. In addition, future studies should pay increased attention to the potential of detecting precursor lesions.

Cited by 192 publications

References 105 publications

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

Clinical significance of HSP27 expression in colorectal cancer

Biomarkers for Cancer Risk, Early Detection, and Prognosis: The Validation Conundrum

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