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chemoresistance. [100] Signifi cant associations were found pathogenesis of the disease and of the biological basis
among the biomarkers, which support the chaperone for outcome disparities. Furthermore, the consequent
function of CD147, as corroborated by others. We emergence of UBC biomarkers will allow us to identify
[94]
also observed that CD147, MCT1, and MCT4 were patients at increased risk of recurrence, progression,
upregulated [Figure 1e-g], being signifi cantly associated metastasis, and/or chemorefractoryness, informing
with a poor clinicopathological profi le, namely, us about more effi cient treatment and surveillance
advancing stage, grade, type of lesion, and occurrence strategies. In addition, biomarkers may improve
of LVI. Moreover, MCT1 and CD147 overexpressions prediction of response to treatment and guide us to an
were associated with poor prognosis, particularly in cases era of personalized medicine and targeted therapy. In
that were positive for both biomarkers. Interestingly, fact, classical diagnostic and prognostic instruments,
when we selected patients who received platinum-based such as risk stratifi cation tables, [109,110] nomograms, [111,112]
chemotherapy, the prognosis was signifi cantly worse for and artifi cial neural networks, [113,114] would undoubtedly
those with MCT1- and CD147-positive tumors. Probably, refi ne diagnosis, prognosis, and therapeutic decisions with
MCT1 cooperates with CD147 in the promotion of the inclusion of prognostic and predictive biomarkers.
a chemoresistance phenotype and possibly, of other Several studies have demonstrated the potential impact
functions primarily attributed to CD147. In fact, it appears of developing risk stratifi cation tools that combine
that CD147 maturation is affected by MCT expression. [102] clinicopathological and biological parameters. [101,115,116]
Other authors have identifi ed CD147 expression in UBC Moreover, it seems that integrating a molecular signature
as an independent prognostic biomarker, [103,104] and of biomarkers inherent in different cancer hallmarks
have additionally proposed it as a predictive biomarker improves predictive accuracy over one biomarker
in the setting of cisplatin-containing regimens. [104,105] abnormality, as several biomarkers may help to elucidate
Recently, one group [106] demonstrated the independent individual biological features of tumors. [14,101,117-120] Our
prognostic signifi cance of MCT1 and MCT4 in UBC. previous study on a tumor aggressiveness scoring model,
Those results led us to knock down CD147 expression where we combined analysis of 2 clinicopathological
in a UBC cell line with a cisplatin-resistant phenotype. parameters, stage and grade, with 3 biological parameters,
We found that CD147 depletion was accompanied by a BVI, LVI, and CD147 overexpression, also corroborates
decrease in MCT1 and MCT4 expressions, additionally those premises [Table 1]. [101] In fact, the recent genomic
supporting its chaperone function. Notably, we also profi le of UBC revealed a more complex picture
found an increase in chemosensitivity to cisplatin. than it was previously supposed, with multiple molecular
To the best of our knowledge, this is the fi rst study to subclasses that traverse conventional grade and stage
assess MCT expression and correlation with CD147 groupings. [76,121,122] This leads us to believe that only an
in UBC tissue from platinum-treated patients, and to integrated clinicopathological and molecular signature
characterize UBC chemosensitivity to cisplatin in vitro will refi ne prognostication and therapeutic index for
upon CD147 inhibition. Our fi ndings reveal a major role UBC patients. Therefore, it is important to transpose tests
of CD147 and companions in promoting progression on small groups of patients to large-scale independent
of a UBC-aggressive phenotype, with high glycolytic validation assays, involving multiple institutions so that
activity, contributing to microenvironmental acidifi cation. prospective validations and randomized trials based on the
This enables the malignant cell to demonstrate growth, retrospective outcomes may then proceed. As stated, [123]
migration, invasion, and chemoresistance abilities any newly proposed anticancer strategy must integrate a
that can potentially be bypassed if new approaches of personalized treatment outcome approach, ideally resulting
targeted therapeutic intervention are investigated. Though in a predictive cancer staging system orientated toward
investigation of CD147 and its association with metabolic the patient and the tumor, and a response evaluation
remodeling and chemoresistance is still in a preliminary system with multiple standardized variables.
phase in UBCs, progress has been made in other areas, References
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62 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦