Co-expression patterns of tumor-associated antigen genes by non-small cell lung carcinomas: Implications for immunotherapy

Karanikas, Vaios; Tsochas, Stefanos; Boukas, Konstantinos; Kerenidi, Theodora; Νάκου, Μαρία; Dahabreh, Jubrail; Poularakis, Theodoros; Gourgoulianis, Konstantinos; Germenis, Anastasios E.

doi:10.4161/cbt.7.3.5424

Cited by 20 publications

(18 citation statements)

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“…Surprisingly, we identified and excluded only one gene (TFPI2) due to effects likely related to inflammation (38,39). Furthermore, the coexpression analyses demonstrate that newly identified CTAs largely group together with established CTAs, indicating a similar regulatory mechanism and coordinated expression, which is a known feature of CTAs (22,40,41). This finding was also supported by the methylation analysis of TCGA data.…”

Section: Figure 9 Network Analysis Of Cancer Testis Antigens (Ctas) supporting

confidence: 68%

Profiling cancer testis antigens in non–small-cell lung cancer

Djureinovic¹,

Hallström²,

Horie³

et al. 2016

JCI Insight

104

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Section: Figure 9 Network Analysis Of Cancer Testis Antigens (Ctas) supporting

confidence: 68%

Profiling cancer testis antigens in non–small-cell lung cancer

Djureinovic¹,

Hallström²,

Horie³

et al. 2016

JCI Insight

104

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“…The expression levels of survivin were positively related to those of hTERT in non-small cell lung carcinomas. 18 Yuan et al 19 found that repression of hTERT resulted in the rapid down-regulation of survivin in telomerase-immortalized fibroblasts and tumor cell lines, but not in cells immortalized via an alternative lengthening of telomeres mechanism. The authors concluded that these observations have important therapeutic implications, as telomerase and survivin are both broadly expressed in human cancers.…”

mentioning

confidence: 99%

Expression of Human Telomerase Reverse Transcriptase in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma: An Immunohistochemical Study With Survivin and p53

Wellenhofer¹,

Brustmann²

2012

Archives of Pathology &Amp; Laboratory Medicine

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N Context.-Human telomerase reverse transcriptase (hTERT), an enzyme that enables cells to overcome replicative senescence and to divide indefinitely, is overexpressed in many cancers and their precursor lesions.Objective.-To test whether hTERT expression is related to neoplastic progression and resistance to apoptosis in vulvar epithelia.Design.-Immunoexpression of hTERT was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n = 25), lichen sclerosus (n = 10), high-grade classic vulvar intraepithelial neoplasia (n = 16), differentiated vulvar intraepithelial neoplasia (n = 18), and vulvar invasive keratinizing squamous cell carcinoma (n = 32) and related to survivin and p53 expression. Immunostaining for all factors was scored for moderate and strong intensities with regard to quantity to determine upregulation and overexpression (score 0, 0% immunoreactive cells; score 1+, ,5% immunoreactive cells; score 2+, 5% to 50% immunoreactive cells; score 3+, .50% immunoreactive cells). Score 3+ was considered as overexpression.Results.-Nuclear hTERT immunoexpression was closely related to survivin reactivity, increased from normal vulvar squamous epithelia to lichen sclerosus and to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and invasive keratinizing squamous cell carcinoma (P , .001), and followed the morphologic distribution of atypical squamous epithelial cells. Overexpression of hTERT was comparable to that seen for p53 in invasive keratinizing squamous cell carcinoma (P = .62); significant differences were calculated for differentiated vulvar intraepithelial neoplasia (P = .003) and highgrade classic vulvar intraepithelial neoplasia (P = .001).Conclusion.-Human telomerase reverse transcriptase is upregulated in vulvar intraepithelial neoplasia and invasive keratinizing squamous cell carcinoma compared with nonneoplastic squamous epithelia of the vulva as an apparently early and preinvasive event in the neoplastic transformation, with development of cellular longevity and resistance to apoptosis by survivin activation as associated features, independent of the etiology of vulvar intraepithelial neoplasia.(Arch Pathol Lab Med. 2012;136:1359-1365; doi: 10.5858/arpa.2011-0440-OA) I nvasive squamous cell carcinoma (ISCC) is the most common type of all invasive vulvar cancers. Vulvar intraepithelial neoplasias (VINs) are precancerous changes, defined as proliferative intraepithelial squamous lesions that display abnormal growth, exhibiting lack of cellular maturation and crowding of cells. According to the grade of dysplasia, they are designated as VIN grade 1, 2, or 3. The vast majority of VIN lesions are considered grade 2 or 3, with a distinction between these 2 grades being highly subjective. Basaloid and warty (condylomatous) or classic subtypes of VIN are associated with relatively younger women, and evidence of human papillomavirus (HPV) nucleic acids. A third, ''differentiated'' su...

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“…The statistically significant difference in the concentration of antibodies, observed in the group of NSCLC, obviously represents the effect of extreme values (11.5±15.2 RAU), with only three of these values from patients, being above the upper limit of those detected in normal individuals. This finding becomes even more intriguing considering that survivin was found to be overexpressed in nearly all NSCLC [46] yet, at the same time; this was not accompanied by a detectable anti-survivin CTL response [129].…”

Section: Resultsmentioning

confidence: 99%

“…Institutional Considering that for an antibody response to occur, an antigen needs to be seen by the immune system, resected tissues from 24 patients (NSCLC) were examined for the presence of mRNA transcript expression in a previous study of ours [46]. All the examined patient samples, representing a proportion of those tested for antibodies, expressed variable levels of survivin mRNA transcripts (Table 4).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the humoral immune response against survivin in patients with lung cancer

Khalil¹

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DedicationTo my mother, the source of inspiration, the eternal flame and support, I would like to dedicate this effort and to tell her if it wasn't for you I might have give up before I achieved the goal of my life.To my late father, the hero who put my feet on the track of education and offered a helping hand whenever I tripped on my first step, but did not live long enough to see me achieve my goals, I say: I'm there father, I love you and I wish you were here to see your dreams come true! God bless you. SummaryAutoantibodies have been shown to be present in the circulation of people with various forms of solid tumours before cancer-associated antigens can be detected. Unlike circulating proteins that are shed by bulky tumors, autoantibodies are detectable even when antigen expression is minimal and they can be measured up to 5 years prior to disease detection. They are usually directed against oncoproteins, aberrantly expressed tumour suppression genes, proliferation-associated antigens as well as nuclear antigens.Existing evidence regarding spontaneous anti-survivin humoral responses in lung cancer is inconclusive. Moreover, despite that cancer cell death elicited by radiotherapy and some chemotherapeutic agents seems to be immunogenic, information about the possible effect of treatment on these responses, is lacking. Serum samples from 33 small cell lung cancer (SCLC) and 117 non-small cell lung cancer (NSCLC) patients upon diagnosis, and from 100 controls, were tested by ELISA for anti-survivin antibodies. Cutoff was set to the mean+2SD of controls. 7.7% of NSCLC, none of the SCLC patients and 2% of the controls appeared with elevated antibody levels (OR 3.6, 95% CI 0.7-17.3 for NSCLC, OR 0.6, 95% CI 0.03-12.6 for SCLC). Measurement of antibodies in 76 NCSLC patients post therapies and during their follow-up, revealed 12 NSCLC patients that increased their antibody levels up to 2-38 times, and 7 others that decreased them by 2-8 times. No significant correlation was uncovered between either the antibody levels upon diagnosis or their changes post therapies and during follow-up, and any clinicopathological parameter, their response to treatment and survival. We conclude that survivin does not induce considerable humoral responses in lung cancer. Potentially, however, strong anti-survivin antibody responses can be elicited during the follow-up of the patients, whose clinical significance remains to be elucidated. These findings, together with our previous data concerning survivin expression and the related cytolytic T cell responses in lung cancer, signify a high tolerogenic potential of this tumor-associated antigen.

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Co-expression patterns of tumor-associated antigen genes by non-small cell lung carcinomas: Implications for immunotherapy

Cited by 20 publications

References 47 publications

Profiling cancer testis antigens in non–small-cell lung cancer

Profiling cancer testis antigens in non–small-cell lung cancer

Expression of Human Telomerase Reverse Transcriptase in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma: An Immunohistochemical Study With Survivin and p53

Evaluation of the humoral immune response against survivin in patients with lung cancer

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