Prognostic Value of SPARC Expression in Unresectable NSCLC Treated with Concurrent Chemoradiotherapy

Kurtul, Neslihan; Eroğlu, Celalettin; Ünal, Dilek; Taşdemir, Erdem Arzu; Orhan, Okan; Zararsız, Gökmen; Baran, Münevver; Kaplan, Bünyamin; Kontaş, Olgun

doi:10.7314/apjcp.2014.15.20.8911

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…However, CAFs are of heterogeneous origins, exhibit diverse biological properties, and can promote or inhibit tumorigenesis 37 . Tumor classification systems incorporating CAF expression signatures accurately predict patient outcome 2–5, 38–47 . Similar to the findings reported here, Navab et al .…”

Section: Discussionmentioning

confidence: 99%

Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Schliekelman

Creighton

Baird

et al. 2017

Sci Rep

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Cancer-associated fibroblasts (CAFs) regulate diverse intratumoral biological programs and can promote or inhibit tumorigenesis, but those CAF populations that negatively impact the clinical outcome of lung cancer patients have not been fully elucidated. Because Thy-1 (CD90) marks CAFs that promote tumor cell invasion in a murine model of KrasG12D–driven lung adenocarcinoma (KrasLA1), here we postulated that human lung adenocarcinomas containing Thy-1+ CAFs have a worse prognosis. We first examined the location of Thy-1+ CAFs within human lung adenocarcinomas. Cells that co-express Thy-1 and α-smooth muscle actin (αSMA), a CAF marker, were located on the tumor periphery surrounding collectively invading tumor cells and in perivascular regions. To interrogate a human lung cancer database for the presence of Thy-1+ CAFs, we isolated Thy-1+ CAFs and normal lung fibroblasts (LFs) from the lungs of KrasLA1 mice and wild-type littermates, respectively, and performed global proteomic analysis on the murine CAFs and LFs, which identified 425 proteins that were differentially expressed. Used as a probe to identify Thy-1+ CAF-enriched tumors in a compendium of 1,586 lung adenocarcinomas, the presence of the 425-gene signature predicted a significantly shorter survival. Thus, Thy-1 marks a CAF population that adversely impacts clinical outcome in human lung cancer.

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Section: Discussionmentioning

confidence: 99%

Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Schliekelman

Creighton

Baird

et al. 2017

Sci Rep

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“…Briefly, the number of patients in each study ranged from 36 to 1,093, and a total of 5,939 patients from 11 countries were included in the present meta-analysis. The studies focused on solid tumors, including gastric cancer,11,16-18 esophageal squamous cell carcinoma,19,20 pancreatic cancer,8,21-25 lung cancer,10,26,27 breast cancer,4,9,28 colorectal cancer,29-32 diffuse large B-cell lymphoma,12,33 biliary tract cancer,7 and nasopharyngeal carcinoma 34. The positive rates of SPARC varied among the 9 solid tumors, and in the same tumor type, the positive rates of SPARC expressed in cancer and stromal cells were also different ( Figure 1B ).…”

Section: Resultsmentioning

confidence: 99%

“…Though numerous studies have revealed that SPARC was expressed in different types of cancers, the exact function of SPARC is controversial. Some reports have shown that SPARC may contribute to cell adhesion, angiogenesis and proliferation, and the overexpression of SPARC was associated with tumor metastasis and poor prognosis in biliary tract, pancreatic, breast and non-small cell lung cancers 6-10. However, other studies have reported that SPARC served an inhibitory role in angiogenesis and tumor formation, resulting in favorable prognosis in gastric cancer and diffuse large B-cell lymphoma 11,12.…”

mentioning

confidence: 99%

Prognostic role of secreted protein acidic and rich in cysteine in patients with solid tumors

Chen

et al. 2019

SMJ

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Objectives: To analyze the heterogeneous functions of secreted protein acidic and rich in cysteine (SPARC) from different origins and in different tumor microenvironments with the purpose of determining its clinical significance. Methods: The PubMed, CINAHL, Cochrane, Web of Science and Embase databases were utilized. Studies that focused on the effects of SPARC expression on solid tumor progression and clinical implications were used. The different outcomes including overall survival and disease-free survival were analyzed to evaluate their relations with tumor- and stroma-derived SPARC expression. Results: A total of 26 studies including 5,939 patients were enrolled in the present meta-analysis. Tumor-derived SPARC overexpression was significantly related with poor overall survival (hazard ratio: 1.478; 95% CI: 1.143-1.910; p=0.003), and a similar tendency was also observed in disease-free survival (hazard ratio: 1.476; 95% CI: 0.993-2.195; p=0.054). However, the hazard ratios for overall survival and disease-free survival did not present a statistical trend in stromal SPARC overexpression. Tumor type subgroup analysis revealed marked heterogeneity among outcomes. In pancreatic cancer, SPARC overexpression in the stroma was significantly associated with poorer overall survival and disease-free survival. In colorectal cancer, SPARC overexpression in the stroma was associated with better disease-free survival. Conclusion: For the majority of solid tumors, SPARC in cancer cells may be an unfavorable indicator for long-term survival for patients. As for stromal expression, SPARC indicates a poorer prognosis in pancreatic cancer, but a better disease-free survival in colorectal cancer. Secreted protein acidic and rich in cysteine might be a potential biomarker for solid tumor prognosis.

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“…The same observation was made for rectal cancer 17 . In the study by Kurtul N. et al 18 increased SPARC expression was associated with poor prognosis when patients were treated with nab-paclitaxel and concurrent radiotherapy. In the study by Kaira K. et al 19 a combination of carboplatin and nab-paclitaxel plus radiotherapy was administered as first line in unresectable stage III NSCLC with safety and efficacy in patients ≤65 years of age.…”

Section: Discussionmentioning

confidence: 98%

Nab-paclitaxel as First Line Treatment for NSCLC in Elderly Patients More Than 75 Years Old

et al. 2017

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Introduction: Lung cancer is still the leading cause of cancer among cancer patients. Although there are novel therapies as second line treatment for NSCLC, there is an issue for elderly patients. Patients and Methods: We collected retrospectively data from 60 patients >75 years of age. Thirty of these patients received nab-paclitaxel and first line treatment and were compared to thirty patients that received only best supportive care. Results: The median life of patients at the date of disease progression, although increased by the administration of the drug (92 days versus 70) was not confirmed statistically significantly (Mann-Whitney test: W = 280, p = 0.138). The administration of drug seems to keep stable the biological condition of patients (McNemar's test: χ2 = 0.033, p = 0.99). Patients with chemotherapy the death rate was increased by 50% as compared to those with best supportive care (12 vs 8), the median life until the unfortunate event surpassed statistically significantly the latter (150 days of life as compared to 108, Mann-Whitney test: W = 57.5, p = 0.045). Discussion: Nab-paclitaxel as a monotherapy could be considered as a first line treatment option for patients > 75 years of age without any previous cardiological medical history when compared to best supportive care.

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Prognostic Value of SPARC Expression in Unresectable NSCLC Treated with Concurrent Chemoradiotherapy

Cited by 12 publications

References 27 publications

Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Prognostic role of secreted protein acidic and rich in cysteine in patients with solid tumors

Nab-paclitaxel as First Line Treatment for NSCLC in Elderly Patients More Than 75 Years Old

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