Increased serum levels of KiSS1-derived peptides in non-small cell lung cancer patient liquid biopsies and biological relevance

Gatti, Laura; Rolli, Luigi; Corno, Cristina; Carenini, Nives; Corna, Elisabetta; Ciusani, Emilio; Frigerio, Simona; Pogliani, Simona; Guarino, Carmela; Ravagnani, Ferdinando; Pastorino, Ugo; Sozzi, Gabriella; Macciotta, Alessandra; Verderio, Paolo; Ciniselli, Chiara Maura; Perego, Paola

doi:10.21037/tlcr-22-52

Cited by 5 publications

(15 citation statements)

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“…Because we planned to use apoptosis as readout of the treatment efficacy, apoptosis induction was examined in response to treatment of melanoma cells with the BRAF inhibitor PLX4032 as well as to conventional antitumor agents such as cDDP and TMZ. Although cDDP is not used in melanoma therapy, the literature provides evidence of modulation of apoptosis by cDDP in head and neck and lung cancers ( 9 , 10 ). Thus, cDDP treatment was included in our study.…”

Section: Resultsmentioning

confidence: 99%

“…At first, apoptosis induction following PLX4032 exposure was examined in LM36 and LM36R melanoma cells. Moreover, LM36 and LM36R were exposed for 48 h to two different concentrations of PLX4032 alone or in combination with 500 ng/mL KP54 ( 10 ). A dose-dependent apoptosis induction was observed following the treatment of LM36 and LM36R with PLX4032 ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, since KP54 combined with cDDP has been reported to result in a synergic interaction that potentiates the antitumor activity of cDDP in head and neck squamous cell carcinoma and lung cancer cells ( 9 , 10 ), also the combination PLX4032/cDDP was considered. As expected, cDDP exposure resulted in a dose-dependent induction of apoptotis in LM36 and LM36R.…”

Section: Resultsmentioning

confidence: 99%

“…In this context, studies aimed at clarifying the molecular mechanisms subtending melanoma aggressiveness as well as response to treatment are expected to improve the medical management of this disease. In this study, we focused on the metastasis suppressor gene KiSS1, whose function as a modulator of apoptosis in head and neck and lung cancers has already been demonstrated ( 9 , 10 ). Here, a role for KiSS1 as regulator of the cellular response to vemurafenib in melanoma cell lines all characterized by the BRAF V600E mutation has emerged.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, another study from our research team showed a peculiar modulation of KiSS1 levels in liquid biopsies of non-small cell lung cancer (NSCLC) patients, supporting the potential use of KiSS1 as a biomarker for this tumor. The study also highlights the role played by KiSS1-cleaved peptide KP54 in increasing the apoptosis induced by the treatment with cDDP, envisioning possible implications for the use of KP54 in antitumor therapy of this disease ( 10 ).…”

Section: Introductionmentioning

confidence: 91%

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Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells

Guzzetti,

Corno,

Vergani

et al. 2023

Front. Oncol.

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Metastatic dissemination is still one of the major causes of death of melanoma’s patients. KiSS1 is a metastasis suppressor originally identified in melanoma cells, known to play an important physiological role in mammals’ development and puberty. It has been previously shown that expression of KiSS1 could be increased in lung cancer cells using epigenetic agents, and that KiSS1 could have a pro-apoptotic action in combination with cisplatin. Thus, the aim of the present study was to examine in human melanoma vemurafenib sensitive- and -resistant BRAF mutant cells characterized by different mutational profiles and KiSS1, KiSS1 receptor and KiSS1 drug-induced release, if peptides derived from KiSS1 cleavage, i.e., kisspeptin 54, could increase the sensitivity to vemurafenib of human melanoma, using cellular, molecular and biochemical approaches. We found that kisspeptin 54 increases vemurafenib pro-apoptotic activity in a statistically significant manner, also in drug resistant cellular models. The efficacy of the combination appears to reflect the intrinsic susceptibility of each cell line to PLX4032-induced apoptosis, together with the different mutational profile as well as perturbation of proteins regulating the apoptotic pathway, The results presented here highlight the possibility to exploit KiSS1 to modulate the apoptotic response to therapeutically relevant agents, suggesting a multitasking function of this metastasis suppressor.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

See 3 more Smart Citations

Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells

Guzzetti,

Corno,

Vergani

et al. 2023

Front. Oncol.

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Metastasis suppressor kisspeptin (KISS1) in serum of patients with renal cell carcinoma

Kushlinskii,

Kovaleva,

Gershtein

et al. 2024

Onkourologiâ

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Background. The most important problems in improvement of treatment outcomes in patients with renal cell carcinoma (RCC) are search and validation of molecular markers for its early diagnosis and prognosis. Genes suppressing distant metastasizing but not affecting the primary tumor are called metastasis suppressors. Study of these genes and their products not only improves understanding of the mechanisms of tumor progression, but has practical value for diagnosis, prognosis, and establishment of new molecular targets for antitumor therapy. One of such genes is KISS1 with its product kisspeptin (KISS1) protein.Aim: comparative evaluation of KISS1 concentration in blood serum of practically healthy persons and patients with renal cancer; analysis of correlations between the marker’s level and clinical and morphological characteristics of the disease.Materials and methods. 140 patients with RCC (88 men, 52 women) aged between 29 and 82 years were included in the study. Among them, clear cell RCC was diagnosed in 84 patients, papillary in 38, chromophobe in 18. The control group was comprised of 40 healthy persons of matched age and sex. Pre-treatment KISS1 concentration in blood serum was measured using a direct enzyme immunoassay kit (Kisspeptin 1 – KISS1, Cloud-Clone Corp., USA).Results. Median serum KISS1 concentration in the control group was 51.7 pg/mL which was significantly lower than in the total RCC patient group – 243.6 pg/mL (p <0.0001). ROC analysis of diagnostic value of serum KISS1 level was performed both for the total RCC group and for each of its three histological types. In the total group the sensitivity of the test was 75 %, specificity – 80 % (AUC 0.877; 95 % confidence interval (CI) 0.827–0.927; optimal cut-off level 130.8 pg/mL; р <0.0001). For clear cell RCC, both sensitivity and specificity were 85 % (AUC 0.941; 95 % CI 0.902– 0.979; cut-off 141.8 pg/mL; p <0.0001). In non-clear cell RCC types, sensitivity of this marker was only 58 % while the specificity remained 80 % (for papillary RCC AUC 0.787; 95 % CI 0.684–0.889; cut-off level 135.5 pg/mL; p <0.0001, and for chromophobe RCC AUC 0.774; 95 % CI 0.617–0.929; cut-off level 132.1 pg/mL; p <0.001). KISS1 level increased with disease progression: it is significantly higher at more advanced stages above stage I, and in patients with distant metastases compared to those without metastases. Higher serum KISS1 level is also observed in patients with poorly differentiated high-grade (per Furhman) clear cell RCC and papillary RCC (G3–G4) than in those with well differentiated low-grade (G1–G2) tumors.Conclusion. KISS1 level is significantly increased in patients with RCC compared to healthy controls and is a stagedependent marker of this disease. It has relatively high diagnostic sensitivity and specificity (both 85 %) for the most frequent histological type of RCC – clear cell RCC. Thus, clinical significance of kisspeptin in RCC requires further investigation.

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Metastasis suppressor kisspeptin (KISS1) in the blood serum of lung cancer patients

Gershtein,

Kovaleva,

Kuzmin

et al. 2024

Bûll. sib. med.

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Aim. To conduct a comparative assessment of the content of kisspeptin (KISS1) metastasis suppressor in the blood serum of apparently healthy individuals and patients with lung cancer (LC) and to analyze the associations between the KISS1 level and clinical and pathological characteristics of the disease.Materials and methods. The study included 74 LC patients and 46 apparently healthy individuals. Stage I LC was diagnosed in 8 patients, stage II LC – in 7 patients, stage III LC – in 28 patients, and stage IV LC – in 31 patients. According to the histologic pattern, 32 tumors were characterized as adenocarcinoma, 29 – as squamous-cell carcinoma, 11 – as small-cell LC (SCLC), and 2 – as large-cell lung carcinoma. The pre-treatment KISS1 level in the blood serum was determined using the enzyme-linked immunosorbent assay kit (KISS1, CloudClone Corp., USA).Results. The median serum KISS1 level in LC patients was 213 (range 7.8–716) pg / ml and was significantly higher than in the control group – 83.4 (0–180) pg / ml (p < 0.0001). The ROC analysis of the diagnostic value of serum KISS1 level demonstrated that the sensitivity of the test in relation to the healthy controls was 70% at a cutoff value of 152 pg / ml, and the specificity was 85% (AUC – 0.817; р < 0.0001). In stage I–II LC, the sensitivity did not exceed 50%. The level of KISS1 in the blood serum did not depend on the histologic type of the tumor. No significant differences in the serum KISS1 levels were observed both between non-small cell lung cancer (NSCLC) on the whole and neuroendocrine SCLC and between the main histologic types of NSCLC. The level of KISS1 increased with the disease stage (p < 0.05). However, none of the TNM staging system indices significantly influenced the level of the marker. No differences were found between serum KISS1 levels in patients with central or peripheral localization of the tumor.Conclusion. The KISS1 level was elevated in LC patients compared to healthy controls and was a stage-dependent marker. It has high diagnostic specificity but insufficient sensitivity, especially at early stages of the disease. Based on the results of this study and literature data on the role of KISS1in NSCLC, we conclude that clinical implications of KISS1 in this disease require further research.

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Increased serum levels of KiSS1-derived peptides in non-small cell lung cancer patient liquid biopsies and biological relevance

Cited by 5 publications

References 31 publications

Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells

Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells

Metastasis suppressor kisspeptin (KISS1) in serum of patients with renal cell carcinoma

Metastasis suppressor kisspeptin (KISS1) in the blood serum of lung cancer patients

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