Cancer Biomarkers - Volume 8, issue 6

Authors: Huang, Lisa P. | Adelson, Martin E. | Mordechai, Eli | Trama, Jason P.

Article Type: Research Article

Abstract: Early detection of cervical cancer is critical for a favorable prognosis. Standard cytological detection methods, such as Pap smear, are highly subjective and HPV detection is not a reliable marker for predicting the malignancy potential of cervical lesions. As a result, there is a demand for a diagnostic assay capable of sensitive and specific detection of cervical cancer. In this preclinical exploratory study, qRT-PCR and western blotting were used to assess expression levels of CIP2A and p16INK4a in cervical tissue samples (nnormal adjacent = 23, ntumor = 29). CIP2A was abundantly expressed in cervical cancer cell lines …and was not expressed in normal epithelial cells. CIP2A mRNA levels were higher in cervical tumor tissues in comparison to the level of CIP2A mRNA in normal adjacent tissue from cervical cancer patients. CIP2A protein was specifically expressed in cervical tumor tissues at different cancer grades and stages, and was not observed in normal adjacent tissue. Elevated CIP2A mRNA levels in cervical tissues had a sensitivity of 80% and specificity of 91% and CIP2A protein expression detection had a sensitivity of 83% and specificity of 100%, similar to that of p16INK4a , with no correlation of CIP2A expression with HPV infection, age, race, or other patient characteristics. However the number of samples analyzed in this preliminary study is limited and a large prospective cohort study is necessary to further evaluate CIP2A as a biomarker for cervical cancer. Show more

Keywords: Cervical cancer, cancer biomarker, cancer diagnostic, CIP2A, p16INK4a

DOI: 10.3233/CBM-2011-0220

Citation: Cancer Biomarkers, vol. 8, no. 6, pp. 309-317, 2011

Authors: Liang, Seng | Singh, Manjit | Gam, Lay-Harn

Article Type: Research Article

Abstract: Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of …these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested. Show more

Keywords: Breast cancer, biological markers, ethnicity, hydrophobic proteins, proteomics

DOI: 10.3233/CBM-2011-0221

Citation: Cancer Biomarkers, vol. 8, no. 6, pp. 319-330, 2011

Authors: Karim, Bougatef | Florence, Coulet | Kamel, Rouissi | Nadia, Kourda | Ines, Omrane | Raja, Marrakchi | Sarra, Ben Jileni | Florent, Soubrier | Amel, Ben Ammar-Elgaaied

Article Type: Research Article

Abstract: The Kirsten Rat Sarcoma (KRAS) oncogene has been introduced recently as a genetic biomarker for metastatic sporadic colorectal cancer prior to anti-EGFR treatment. Identifying patients with KRAS mutations that not respond to EGFR targeted therapies require sensitive, rapid and efficacious routine technique. We have attempted to evaluate the efficiency of three conventional methods: direct sequencing, HRM and DHPLC, to detect mutations in codon 12 and 13 of the KRAS exon2 gene. For this first Tunisian study on KRAS, we detected 45.83% of altered KRAS gene among 48 formalin-fixed paraffin-embedded sporadic colorectal adenocarcinoma patients. The use of HRM-sequencing allowed as enlarging …the detected KRAS exon 2 mutations (22/48) in comparison with direct sequencing (17/48). DHPLC was used to confirm results when consensus was not observed between HRM and direct sequencing. This study brings an interesting data concerning an inter-method validation between sequencing and HRM in the investigation of sporadic colorectal cancer biomarker. It also shows that KRAS mutations occur at similar frequencies in Tunisian patients as in other populations; and suggests that the same genes are at play in sporadic CRC cancer, despite ethnic, geographical and environmental differences between countries. Show more

Keywords: Sporadic colorectal cancer, biomarker, KRAS, EGFR, HRM, DHPLC, direct sequencing

DOI: 10.3233/CBM-2011-0222

Citation: Cancer Biomarkers, vol. 8, no. 6, pp. 331-340, 2011

Authors: Vázquez-Vega, Salvador | Sánchez-Suárez, Lilia Patricia | Contreras-Paredes, Adriana | Castellanos-Juárez, Emilio | Peñarroja-Flores, Rubicelia | Lizano-Soberón, Marcela | Andrade-Cruz, Rafael | García-Carrancá, Alejandro | Benítez-Bribiesca, Luis

Article Type: Research Article

Abstract: The Papanicolaou test (Pap) has been responsible for a significant reduction of cervical cancer-related morbimortality. In order to increase its sensitivity and specificity new markers have been studied and incorporated to cytological and histological methods for diagnosis for cervical cancer, such as p16INK4A that has been considered the immunocytochemical marker of choice for detection of HPV related cancers. We considered that p14ARF could be a complementary marker in order to improve the accuracy of cytological diagnosis because its genetic proximity to p16INK4A . We performed a systematic analysis of several putative cervical cancer markers in order to evaluate …their performance in the detection of malignancy, in comparison with p16INK4A and p14ARF , using immunocytochemistry (ICC), immunofluorescence (IF) and Western blot analyses. Most markers were non-specific and could not discriminate HPV infected cancer cell lines from other non HPV malignant. In contrast, nuclear co-expression of p16INK4A and p14ARF was observed only in HPV-transformed cancer cell lines. Notably, in C-33A cervical cancer cells (HPV negative), p14ARF was present in the nucleoli, but p16INK4A was conspicuously absent from the nuclei of these cells. We conclude that both markers; p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer. Show more

Keywords: Cervical cancer cell lines, cervical cancer markers, p14ARF, p16INK4A

DOI: 10.3233/CBM-2011-0223

Citation: Cancer Biomarkers, vol. 8, no. 6, pp. 341-350, 2011

Authors: Singh, Arvind P. | Pant, Mohan C. | Ruwali, Munindra | Shah, Parag P. | Prasad, Rajendra | Mathur, Neeraj | Parmar, Devendra

Article Type: Research Article

Abstract: The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis …revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma. Show more

Keywords: Lung cancer, risk, CYP1A2, polymorphism, tobacco

DOI: 10.3233/CBM-2011-0224

Citation: Cancer Biomarkers, vol. 8, no. 6, pp. 351-359, 2011