Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers

Blumenthal, Rosalyn D.; Leon, E.J.; Hansen, Hans J.; Goldenberg, David M.

doi:10.1186/1471-2407-7-2

Cited by 212 publications

(221 citation statements)

References 40 publications

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“…However, SLIT2 has been shown to be associated with metastases in other cancers [23,24]. CEACAM6 is an oncogene that has been found to be associated with tumor progression and metastasis in pancreatic, breast, colon, lung, and gastric cancer [25,26] and to be associated with poor outcome in RCC [16]. Similar to our observations in ccRCC, CEACAM6 has been shown to be upregulated in colon metastasis in comparison to primary tumors [25].…”

Section: Discussionsupporting

confidence: 80%

“…CEACAM6 is an oncogene that has been found to be associated with tumor progression and metastasis in pancreatic, breast, colon, lung, and gastric cancer [25,26] and to be associated with poor outcome in RCC [16]. Similar to our observations in ccRCC, CEACAM6 has been shown to be upregulated in colon metastasis in comparison to primary tumors [25]. Overall, these genes represent possible targets for metastatic ccRCC and deserve further attention.…”

Section: Discussionsupporting

confidence: 77%

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Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes

Serie²,

Parasramka³

et al. 2017

Annals of Oncology

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Background: The majority of renal cell carcinoma (RCC) studies analyze primary tumors, and the corresponding results are extrapolated to metastatic RCC tumors. However, it is unknown if gene expression profiles from primary RCC tumors differs from patient-matched metastatic tumors. Thus, we sought to identify differentially expressed genes between patient-matched primary and metastatic RCC tumors in order to understand the molecular mechanisms underlying the development of RCC metastases. Patients and methods:We compared gene expression profiles between patient-matched primary and metastatic RCC tumors using a two-stage design. First, we used Affymetrix microarrays on 15 pairs of primary RCC [14 clear cell RCC (ccRCC), 1 papillary] tumors and patient-matched pulmonary metastases. Second, we used a custom NanoString panel to validate seven candidate genes in an independent cohort of 114 ccRCC patients. Differential gene expression was evaluated using a mixed effect linear model; a random effect denoting patient was included to account for the paired data. Third, The Cancer Genome Atlas (TCGA) data were used to evaluate associations with metastasis-free and overall survival in primary ccRCC tumors.Results: We identified and validated up regulation of seven genes functionally involved in the formation of the extracellular matrix (ECM): DCN, SLIT2, LUM, LAMA2, ADAMTS12, CEACAM6 and LMO3. In primary ccRCC, CEACAM6 and LUM were significantly associated with metastasis-free and overall survival (P < 0.01). Conclusions:We evaluated gene expression profiles using the largest set to date, to our knowledge, of patient-matched primary and metastatic ccRCC tumors and identified up regulation of ECM genes in metastases. Our study implicates up regulation of ECM genes as a critical molecular event leading to visceral, bone and soft tissue metastases in ccRCC.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 77%

Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes

Serie²,

Parasramka³

et al. 2017

Annals of Oncology

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“…29,30 CEACAM5 is a glycosylphosphatidylinositol-anchored protein member of the immunoglobulin supergene family and has been seen to be differentially expressed among lung histological types. 31 TRIM29 contains multiple zinc-finger motifs and a leucine zipper motif and thus may act as a transcriptional regulatory factor. Though little is known of its function in lung carcinogenesis, it has been noted as being differentially expressed between pancreatic ductal and chronic pancreatitis and is a consistent member of 'basal' breast carcinoma classifiers identified in gene expression profiling experiments.…”

Section: Discussionmentioning

confidence: 99%

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Ring¹,

Seitz

Beck

et al. 2009

Modern Pathology

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Malignant epithelial lung carcinoma can be subclassified by histology into several tumor types, including adenocarcinoma and squamous cell carcinoma. The need for a uniform method of classifying lung carcinomas is growing as clinical trials reveal treatment and side effect differences associated with histological subtypes. Diagnosis is primarily performed by morphological assessment. However, the increased use of needle biopsy has diminished the amount of tissue available for interpretation. These changes in how lung carcinomas are diagnosed and treated suggest that the development of improved molecular-based classification tools could improve patient management. We used a 551-patient surgical specimen lung carcinoma retrospective cohort from a regional hospital to assess the association of a large number of proteins with histological type by immunohistochemistry. Five of these antibodies, targeting the proteins TRIM29, CEACAM5, SLC7A5, MUC1, and CK5/6, were combined into one test using a weighted algorithm trained to discriminate adenocarcinoma from squamous cell carcinoma. Antibody-based classification on 600 lM tissue array cores with the fiveantibody test was compared to standard histological evaluation on surgical specimens in three independent lung carcinoma cohorts (combined population of 1111 patients). In addition, the five-antibody test was tested against the two-marker panel thyroid transcription factor-1 (TTF-1) and TP63. Both the five-antibody test and TTF-1/TP63 panel had similarly low misclassification rates on the validation cohorts compared to morphological-based diagnosis (4.1 vs 3.5%). However the percentage of patients remaining unclassifiable by TTF-1/TP63 (22%, 95% CI: 20-25%) was twice that of the five-antibody test (11%, 95% CI: 8-13%). The results of this study suggest the five-antibody test may have an immediate function in the clinic for helping pathologists distinguish lung carcinoma histological types. The results also suggest that if validated in prospectively defined clinical trials this classifier might identify candidates for targeted therapy that are overlooked with current diagnostic approaches.

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“…With the milatuzumab-doxorubicin conjugate having inferior therapeutic results in 2 of the solid tumor xenografts, the focus shifted to comparing the milatuzumab-SN-38 conjugates with SN-38 conjugates prepared with other humanized antibodies against Trop-2 (hRS7) or CEACAM6 (hMN-15), which are more highly expressed on the surface of many solid tumors (38,39). Three additional xenograft models were examined.…”

Section: In Vivo Therapy For Human Tumor Xenograftsmentioning

confidence: 99%

Milatuzumab–SN-38 Conjugates for the Treatment of CD74+ Cancers

Govindan

Cardillo

Sharkey

et al. 2013

Molecular Cancer Therapeutics

117

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CD74 is an attractive target for antibody-drug conjugates (ADC), because it internalizes and recycles after antibody binding. CD74 mostly is associated with hematologic tumors but is expressed also in solid cancers. Therefore, ADCs of the humanized anti-CD74 antibody, milatuzumab, were examined for the therapy of CD74-expressing solid tumors. Milatuzumab-doxorubicin and two milatuzumab-SN-38 conjugates with cleavable linkers, differing in their stability in serum and how they release SN-38 in the lysosome, were prepared. CD74 expression was determined by flow cytometry and immunohistology. In vitro cytotoxicity and in vivo therapeutic studies were conducted in the human cancer cell lines A-375 (melanoma), HuH-7 and Hep-G2 (hepatoma), Capan-1 (pancreatic), NCI-N87 (gastric), and Raji Burkitt lymphoma. The milatuzumab-SN-38 ADC was compared with SN-38 ADCs prepared with anti-Trop-2 and anti-CEACAM6 antibodies in xenografts expressing their target antigens. Milatuzumab-doxorubicin was most effective in the lymphoma model, whereas in A-375 and Capan-1 solid tumors, only milatuzumab-SN-38 showed a therapeutic benefit. Despite much lower surface expression of CD74 than Trop-2 or CEACAM6, milatuzumab-SN-38 had similar efficacy in Capan-1 as anti-Trop-2-SN-38, but in NCI-N87, anti-CEACAM6 and anti-Trop-2 conjugates were superior. Studies in two hepatoma lines at a single dose level showed significant benefit over saline controls but not against an irrelevant immunoglobulin G conjugate. CD74 is a suitable target for ADCs in some solid tumor xenografts, with efficacy largely influenced by uniformity of CD74 expression and with SN-38 conjugates providing the best therapeutic responses; SN-38 conjugates were preferable in solid cancers, whereas doxorubicin ADC was better in lymphoma tested. Mol Cancer Ther; 12(6); 968-78. Ó2013 AACR.

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Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers

Cited by 212 publications

References 40 publications

Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes

Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Milatuzumab–SN-38 Conjugates for the Treatment of CD74+ Cancers

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