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In Search of the Altering Salivary Proteome in Metastatic Breast and Ovarian Cancer

ABSTRACT: Breast and ovarian cancers, the most common cancers in women in India. Metastatic organotropism is a non-random, predetermined process which represents a more lethal and advanced form of cancer with increased mortality rate. In an attempt to study organotropism, salivary proteins were analyzed by mass spectrometry indicative of pathophysiology of breast and ovarian cancers compared to healthy and ovarian chemotherapy subjects. Collectively, 646 proteins were identified, of which 409 proteins were confidently identified across all four groups. Network analysis of up-regulated proteins such as coronin-1A, hepatoma derived growth factor, vasodilator-stimulated phosphoprotein (VASP), and cofilin in breast cancer and proteins like coronin-1A, destrin and HSP90α in ovarian cancer were functionally linked and were known to regulate cell proliferation and migration. Additionally, proteins namely VASP, coronin-1A, stathmin and suprabasin were confidently identified in ovarian chemotherapy subjects, possibly in response to combined paclitaxel and carboplatin drug therapy to ovarian cancer. In summary, this proteomic study was performed to identify a pattern of differentially expressed salivary proteins as indicators of metastatic organotropism potential of breast and ovarian cancers, as well as their response to neoadjuvant (paclitaxel and carboplatin) drugs therapy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

DISEASE(S): Breast Cancer

SUBMITTER: Kuldeep Giri

LAB HEAD: Kiran Ambatipudi

PROVIDER: PXD011541 | Pride | 2020-05-26

REPOSITORIES: Pride

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In search of the altering salivary proteome in metastatic breast and ovarian cancers.

Giri Kuldeep K Mehta Anurag A Ambatipudi Kiran K

FASEB bioAdvances 20190130 3

Breast and ovarian cancers, the most common cancers in women in India, are expected to rise in the next decade. Metastatic organotropism is a nonrandom, predetermined process which represents a more lethal and advanced form of cancer with increased mortality rate. In an attempt to study organotropism, salivary proteins were analyzed by mass spectrometry indicative of pathophysiology of breast and ovarian cancers and were compared to healthy and ovarian chemotherapy subjects. Collectively, 646 pr ...[more]

PMID: 32123828

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Project description:Purpose: Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Most of these patients are treated with platinum-based chemotherapies, but there is no biomarker model to guide their responses to these therapeutic agents. We have developed and independently tested our novel multivariate molecular predictors for forecasting patients' responses to individual drugs on a cohort of 58 ovarian cancer patients. Experimental Design: We adapted and applied the previously-published COXEN algorithm to develop molecular predictors for therapeutic responses of patients' tumors based on expression signatures derived from the NCI-60 in vitro drug activities and genomic expression data. Genome-wide candidate biomarkers were first triaged by examining expression patterns of frozen and formalin-fixed paraffin embedded (FFPE) tissue samples. We then identify initial drug sensitivity biomarkers for carboplatin and paclitaxel, respectively. These biomarkers were further narrowed by examining concordant expression patterns between cell lines and a historical set of ovarian cancer patients. Multivariate predictors were obtained from the NCI-60 cell lines and refined using historical patient cohorts. To independent validate these molecular predictors, we performed genome-wide profiling on FFPE samples of 58 ovarian cancer patients obtained prior to adjuvant chemotherapy. Results: Carboplatin predictor significantly stratified platinum sensitive and resistant patients (p = 0.019) with sensitivity = 93%, specificity = 33%, PPV = 65%, and NPV = 78%. Paclitaxel predictor also significantly stratified patients' responses (p = 0.033) with sensitivity = 96%, specificity = 26%, PPV = 61%, and NPV = 86%. The combination predictor for platinum-taxane combination demonstrated a significant survival difference between the predicted responders and nonresponders with median survival of 12.9 months vs. 8.1 months (p = 0.045). Conclusions: COXEN predictors successfully stratified platinum resistance and taxane response in this retrospective cohort, especially based on their FFPE tumor samples. Accurate prediction of chemotherapeutic response, especially to platinum agents is highly clinically relevant and could alter primary management of ovarian cancer. Gene expression data from 58 stage III-IV ovarian cancer patients treated with Carboplatin and Taxol agents

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