The Clinical Utility of Serum CXCR-2 Assessment in Colorectal Cancer (CRC) Patients

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

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Assessing the clinical utility of genetic risk scores for targeted cancer screening

Journal of Translational Medicine ◽

10.1186/s12967-020-02699-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Carly A. Conran ◽

Zhuqing Shi ◽

William Kyle Resurreccion ◽

Rong Na ◽

Brian T. Helfand ◽

...

Keyword(s):

Colorectal Cancer ◽

Primary Care ◽

High Risk ◽

Risk Score ◽

Genetic Risk ◽

Clinical Utility ◽

Low Risk ◽

Risk Scores ◽

Average Risk ◽

Genetic Risk Scores

Abstract Background Genome-wide association studies have identified thousands of disease-associated single nucleotide polymorphisms (SNPs). A subset of these SNPs may be additively combined to generate genetic risk scores (GRSs) that confer risk for a specific disease. Although the clinical validity of GRSs to predict risk of specific diseases has been well established, there is still a great need to determine their clinical utility by applying GRSs in primary care for cancer risk assessment and targeted intervention. Methods This clinical study involved 281 primary care patients without a personal history of breast, prostate or colorectal cancer who were 40–70 years old. DNA was obtained from a pre-existing biobank at NorthShore University HealthSystem. GRSs for colorectal cancer and breast or prostate cancer were calculated and shared with participants through their primary care provider. Additional data was gathered using questionnaires as well as electronic medical record information. A t-test or Chi-square test was applied for comparison of demographic and key clinical variables among different groups. Results The median age of the 281 participants was 58 years and the majority were female (66.6%). One hundred one (36.9%) participants received 2 low risk scores, 99 (35.2%) received 1 low risk and 1 average risk score, 37 (13.2%) received 1 low risk and 1 high risk score, 23 (8.2%) received 2 average risk scores, 21 (7.5%) received 1 average risk and 1 high risk score, and no one received 2 high risk scores. Before receiving GRSs, younger patients and women reported significantly more worry about risk of developing cancer. After receiving GRSs, those who received at least one high GRS reported significantly more worry about developing cancer. There were no significant differences found between gender, age, or GRS with regards to participants’ reported optimism about their future health neither before nor after receiving GRS results. Conclusions Genetic risk scores that quantify an individual’s risk of developing breast, prostate and colorectal cancers as compared with a race-defined population average risk have potential clinical utility as a tool for risk stratification and to guide cancer screening in a primary care setting.

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EJS-1 Clinical utility of analysing ctDNA in patients with metastatic colorectal cancer

Annals of Oncology ◽

10.1016/j.annonc.2021.05.364 ◽

2021 ◽

Vol 32 ◽

pp. S230

Author(s):

Josep Tabernero

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Clinical Utility

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The Clinical Utility of the Combination of T Stage and Venous Invasion to Predict Survival in Patients Undergoing Surgery for Colorectal Cancer

Annals of Surgery ◽

10.1097/sla.0000000000000229 ◽

2014 ◽

Vol 259 (6) ◽

pp. 1156-1165 ◽

Cited By ~ 33

Author(s):

Campbell S. D. Roxburgh ◽

Donald C. McMillan ◽

Colin H. Richards ◽

Manal Atwan ◽

John H. Anderson ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Utility ◽

Venous Invasion ◽

T Stage

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Abstract 1353: The clinical utility of ctDNA in colorectal cancer validated by multiregional sequencing and protein analysis

10.1158/1538-7445.sabcs18-1353 ◽

2019 ◽

Author(s):

Mizunori Yaegashi ◽

Takeshi Iwaya ◽

Masashi Fujita ◽

Zhenlin Ju ◽

Doris Siwak ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Utility ◽

Protein Analysis

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Application of Genetically-Engineered Anti-CEA Antibodies for Potential Immunotherapy of Colorectal Cancer

The International Journal of Biological Markers ◽

10.1177/172460089200700315 ◽

1992 ◽

Vol 7 (3) ◽

pp. 203-209 ◽

Cited By ~ 4

Author(s):

N. Hardman ◽

B. Murray ◽

M. Zwickl ◽

F. Kolbinger ◽

G. Pluschke

Keyword(s):

Colorectal Cancer ◽

Clinical Utility ◽

Malignant Disease ◽

Genetic Manipulation ◽

Repeated Administration ◽

Genetically Engineered ◽

Cytotoxic Agents ◽

Human Colorectal Cancer ◽

In Vivo Diagnosis

Hitherto anti-CEA monoclonal antibodies (MAbs), normally of mouse origin, have been used primarily for clinical diagnosis of colorectal cancer, either as a tumor marker in serum to monitor tumor recurrence, or latterly as a means to localize in vivo CEA-bearing tumors and metastases in patients. In vivo diagnosis using mouse anti-CEA MAbs has so far had limited clinical utility because the antibodies elicit a strong anti-mouse immunoglobulin immune response on repeated administration in man. This problem has been addressed by the development of various strategies for “humanization” of mouse anti-CEA MAbs by genetic manipulation of immunoglobulin genes. Such humanized, engineered antibodies markedly attenuate the antigenic response directed against the MAb, such that safe, repeated administration to patients has become feasible. Such humanized anti-CEA antibodies can thus be radioactively-labelled and applied for in vivo monitoring and detection of recurrent malignant disease, or used for therapeutic strategies which similarly take advantage of the ability of the antibodies to target cytotoxic agents selectively to tumor cells. The application of these novel procedures for manipulating MAb structure presents entirely new opportunities for diagnosis and treatment of human colorectal cancer.

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