p16<sup>INK4a</sup> overexpression as a predictor of survival in ocular surface squamous neoplasia

Chauhan, Sheetal; Sen, Seema; Sharma, Aruna; Kashyap, Seema; Tandon, Radhika; Bajaj, Mandeep S; Vanathi, Murugesan; Chauhan, Shyam S.

doi:10.1136/bjophthalmol-2017-311276

Cited by 16 publications

(9 citation statements)

References 28 publications

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“…It is thought that the breakdown of the human body’s immune surveillance against the tumor creates a “permissive environment” for other risk factors to trigger malignant transformation of the epithelial cells [ 39 ]. For example, HPV infection, which is associated with HPV-induced inhibition of the tumor-suppressor protein retinoblastoma (Rb), may interact synergistically with sunlight exposure, which can cause UV radiation-related DNA damage, including the formation of pyrimidine dimers (CC > TT) and epigenetic changes in the p16 gene promoter [ 48 ], and lead to triggering of the neoplastic transformation of the cell lineage.…”

Section: Risk Factors and Pathogenesismentioning

confidence: 99%

“…In terms of the T classification, in 2013, Shields et al noted that the T classification, based on the AJCC seventh edition, was not predictive of surgical failure [ 135 ]; however, several following reports have correlated the recurrence rate to the T category, albeit reporting highly heterogeneous groups of patients [ 147 , 149 , 158 , 159 ]. Recently, the overexpression of the tumor-suppressor gene p16 INK4a has been identified as a biomarker of diffuse growth pattern, early age of presentation (< 50 years), and metastatization in late T stages [ 48 ].…”

Section: Prognosismentioning

confidence: 99%

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Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

et al. 2018

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Ocular surface squamous neoplasia (OSSN) is the most common non-pigmented malignancy of the ocular surface and is represented in a wide range of histologic diagnoses, ranging from mild epithelial dysplasia to invasive squamous carcinoma. Although surgical excision is still the gold standard for OSSN treatment, interest in conservative medical approaches is steadily growing. We have reviewed all of the literature on OSSN published in English in the MEDLINE database up to May 2018, using the keywords “ocular surface squamous neoplasia,” “squamous conjunctival carcinoma,” and “conjunctival carcinoma in situ,” with the aim to provide a comprehensive review of the most recent evidence on this distinct clinical entity.

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Section: Risk Factors and Pathogenesismentioning

confidence: 99%

Section: Prognosismentioning

confidence: 99%

Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

et al. 2018

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“…The etiology of this disease, and particularly of primary conjunctival cancer, is still not well defined. Causes underlying its development are likely multifactorial, being influenced by age, sex, ethnicity, systemic diseases, and environmental factors [7][8][9][10][11][12]. Conjunctival cancers can cause vision loss, metastasis, and eventually death [13].…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Epidemiological Analysis and Prognosis of Conjunctival Cancer in the Past Twenty Years: A Population‐Based Retrospective Study Using SEER Data

Diao

Huo

et al. 2020

BioMed Research International

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Epidemiological studies of malignant primary conjunctival tumors are rare. We extracted data pertaining to primary site-labeled conjunctival cancer patients present within the Surveillance, Epidemiology, and End Results (SEER) database from 1992 to 2001 and from 2002 to 2011. The Kaplan-Meier approach was used for comparisons of overall survival (OS) between patients, while OS-related risk factors were identified via a Cox proportional hazards regression approach. We then constructed a nomogram that could be used to predict the 3- and 5-year OS, with the accuracy of this predictive model based on receiver operating characteristic (ROC) curve. We observed a significant reduction in age-adjusted incidence of conjunctival cancer in the 50-69-year-old age group of the 2002-2011 cohort relative to the 1992-2001 cohort (APC, P<0.05). There were no significant differences in OS between the 1992-2001 and 2002-2011 conjunctival cancer patient cohorts. Being ≥30 years old (P<0.05), male (P<0.001), single (P<0.05), divorced (P<0.001), or widowed (P<0.001) were all associated with an increased OS-related risk of primary conjunctival cancer (1992-2011). Our nomogram was able to accurately predict 3- and 5-year OS in conjunctival cancer patients. In verification mode, the 3-year area under the curve (AUC) was 0.697 and the 5-year AUC was 0.752. We found that age, sex, and marital status were all associated with primary conjunctival cancer survival. Our results further suggest that conjunctival cancer incidence and survival rates have been relatively stable over the last two decades, and using these data, we were able to generate a satisfactory risk prediction model for this disease.

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Section: Discussionmentioning

confidence: 99%

“…It has been reported that several tumor suppressors are overexpressed in cancer (28,29). For example, p16 lnk4a was upregulated in many human tumors and functioned as a tumor suppressor (28). Accumulating evidence shows that oncogeneinduced senescence can occur in response to oncogenic insults and is considered an important tumor suppressor mechanism (30).…”

Section: Discussionmentioning

confidence: 99%

Keratin 17 Suppresses Cell Proliferation and Epithelial-Mesenchymal Transition in Pancreatic Cancer

et al. 2020

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Keratin 17 (K17), a member of type I acidic epithelial keratin family, has been reported to be upregulated in many malignant tumors and to be involved in promoting the development of tumors. However, the precise role of K17 in progression of pancreatic cancer is still unknown. In this study, we found that K17 expression was highly expressed in pancreatic cancer tissues and cell lines and that upregulated expression was associated with the pathological grade and poor prognosis. K17 expression served as an independent predictor of pancreatic cancer survival. Meanwhile, we showed that knocking down K17 induced pancreatic cancer cell proliferation, colony formation and tumor growth in xenografts in mice. However, K17 upregulation inhibited pancreatic cancer cell proliferation and colony formation. Further mechanistic study revealed that K17 knockdown promoted cell cycle progression by upregulating CyclinD1 expression and repressed cell apoptosis. However, K17 upregulation suppressed cell cycle progression by decreasing CyclinD1 expression, and induced apoptosis by increasing the levels of cleaved Caspase3. In addition, K17 knockdown promoted pancreatic cancer cell migration and invasion, but K17 upregulation suppressed cell migration and invasion. Moreover, knocking down K17 promoted epithelial-mesenchymal transition (EMT) in pancreatic cancer cell by inhibiting E-cadherin expression and inducing Vimentin expression, and the effects of K17 upregulation were opposite to that of K17downregulation. Taken together, our findings suggest that K17 functions as a potential tumor suppressor, even though it is upregulated in pancreatic cancer.

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p16^INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia

Abstract: OSSN patients presenting at an advanced AJCC stage with p16 overexpression may require more aggressive treatment. Epigenetic inactivation of the gene due to sunlight exposure could be responsible for pathogenesis of OSSN.

Cited by 16 publications

References 28 publications

Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

[Retracted] Epidemiological Analysis and Prognosis of Conjunctival Cancer in the Past Twenty Years: A Population‐Based Retrospective Study Using SEER Data

Keratin 17 Suppresses Cell Proliferation and Epithelial-Mesenchymal Transition in Pancreatic Cancer

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p16INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia

Abstract: OSSN patients presenting at an advanced AJCC stage with p16 overexpression may require more aggressive treatment. Epigenetic inactivation of the gene due to sunlight exposure could be responsible for pathogenesis of OSSN.

Cited by 16 publications

References 28 publications

Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

[Retracted] Epidemiological Analysis and Prognosis of Conjunctival Cancer in the Past Twenty Years: A Population‐Based Retrospective Study Using SEER Data

Keratin 17 Suppresses Cell Proliferation and Epithelial-Mesenchymal Transition in Pancreatic Cancer

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p16^INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia