Article Data

  • Views 245
  • Dowloads 132

Original Research

Open Access

Prognostic role and therapeutic implications of phosphatidylinositol transfer protein cytoplasmic 1 in primary prostate cancer

  • Jianming Lu1,†
  • Yunze Fang2,†
  • Jiexin Luo2,†
  • Runxin Zhou3
  • Le Zhang4
  • Chao Cai5
  • Zhengguo Cao2,*,
  • Rujun Mo2,3,6,*,

1Department of Andrology, Guangzhou First People’s Hospital, Guangzhou Medical University, 510180 Guangzhou, Guangdong, China

2Department of Urology, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), 523059 Dongguan, Guangdong, China

3Graduate School, Guangdong Medical University, 524002 Zhanjiang, Guangdong, China

4Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA 92521, USA

5Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, 510230 Guangzhou, Guangdong, China

6Department of Urology, Dongguan People’s Hospital, Guangdong Medical University, 523059 Dongguan, Guangdong, China

DOI: 10.22514/jomh.2024.194 Vol.20,Issue 11,November 2024 pp.136-146

Submitted: 12 June 2024 Accepted: 18 July 2024

Published: 30 November 2024

*Corresponding Author(s): Zhengguo Cao E-mail: zgcao2023@smu.edu.cn
*Corresponding Author(s): Rujun Mo E-mail: rmo@smu.edu.cn

† These authors contributed equally.

Abstract

Phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1) has been implicated in some tumor types, but its role in primary prostate cancer (PCa) remains unexplored. This study investigates the prognostic significance of PITPNC1 in PCa. RNA sequencing (RNA-seq), mutation data and clinical information on PCa cohorts were retrieved from the The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases. Data analysis revealed that PITPNC1 expression was significantly lower in PCa tissues compared to benign tissues, and this reduced expression correlated with earlier biochemical recurrence and decreased overall survival. Functional enrichment analysis indicated that PITPNC1 activates pathways related to cell adhesion and immune receptor signaling while inhibiting RNA metabolism pathways. Additionally, high Tumor Protein P53 (TP53) mutation frequency was observed in the low PITPNC1 expression group. In immunotherapy cohorts, lower PITPNC1 expression was associated with poorer outcomes. Furthermore, Rucaparib was identified as a potential therapeutic agent for patients with low PITPNC1 expression. Collectively, we identified PITPNC1 as a promising prognostic marker in PCa. Its expression levels can predict immunotherapy responses, and it holds potential as a target for precision therapies.


Keywords

Prostate cancer; PITPNC1; Biochemical recurrence; TP53; Immunotherapy


Cite and Share

Jianming Lu,Yunze Fang,Jiexin Luo,Runxin Zhou,Le Zhang,Chao Cai,Zhengguo Cao,Rujun Mo. Prognostic role and therapeutic implications of phosphatidylinositol transfer protein cytoplasmic 1 in primary prostate cancer. Journal of Men's Health. 2024. 20(11);136-146.

References

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023; 73: 17–48.

[3] Yuan MW, Wang HH, Duan RF, Xu KP, Hu SY, Qiao YL, et al. Analysis on cancer incidence and mortality attributed to human papillomavirus infection in China, 2016. Chinese Journal of Epidemiology. 2022; 43: 702–708. (In Chinese)

[4] Alberti A, Nicoletti R, Castellani D, Yuan Y, Maggi M, Dibilio E, et al. Patient-reported outcome measures and experience measures after active surveillance versus radiation therapy versus radical prostatectomy for prostate cancer: a systematic review of prospective comparative studies. To be published in European Urology Oncology. 2024. [Preprint].

[5] Asso RN, Degrande FAM, Fernandes da Silva JL, Leite ETT. Postoperative radiotherapy in prostate cancer: when and how?—An update review. Cancer Radiother. 2022; 26: 742–748.

[6] Sargos P, Leduc N, Giraud N, Gandaglia G, Roumiguié M, Ploussard G, et al. Deep neural networks outperform the CAPRA score in predicting biochemical recurrence after prostatectomy. Frontiers in Oncology. 2020; 10: 607923.

[7] Van den Broeck T, van den Bergh RCN, Arfi N, Gross T, Moris L, Briers E, et al. Prognostic value of biochemical recurrence following treatment with curative intent for prostate cancer: a systematic review. European Urology. 2019; 75: 967–987.

[8] Hong JH, Liang ST, Wang AS, Yeh CM, Huang HP, Sun CD, et al. LMNB1, a potential marker for early prostate cancer progression. American Journal of Cancer Research. 2022; 12: 3390–3404.

[9] Rizzo A, Santoni M, Mollica V, Fiorentino M, Brandi G, Massari F. Microbiota and prostate cancer. Seminars in Cancer Biology. 2022; 86: 1058–1065.

[10] Rosellini M, Santoni M, Mollica V, Rizzo A, Cimadamore A, Scarpelli M, et al. Treating prostate cancer by antibody-drug conjugates. International Journal of Molecular Sciences. 2021; 22: 1551.

[11] Rizzo A, Mollica V, Cimadamore A, Santoni M, Scarpelli M, Giunchi F, et al. Is there a role for immunotherapy in prostate cancer? Cells. 2020; 9: 2051.

[12] Guven DC, Sahin TK, Erul E, Rizzo A, Ricci AD, Aksoy S, et al. The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Frontiers in Molecular Biosciences. 2022; 9: 1039121.

[13] Sahin TK, Rizzo A, Aksoy S, Guven DC. Prognostic significance of the royal marsden hospital (RMH) score in patients with cancer: a systematic review and meta-analysis. Cancers. 2024; 16: 1835.

[14] Entrialgo-Cadierno R, Cueto-Ureña C, Welch C, Feliu I, Macaya I, Vera L, et al. Correction: the phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer. Molecular Cancer. 2023; 22: 97.

[15] Garner K, Hunt AN, Koster G, Somerharju P, Groves E, Li M, et al. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) binds and transfers phosphatidic acid. Journal of Biological Chemistry. 2012; 287: 32263–32276.

[16] Halberg N, Sengelaub CA, Navrazhina K, Molina H, Uryu K, Tavazoie SF. PITPNC1 recruits RAB1B to the golgi network to drive malignant secretion. Cancer Cell. 2016; 29: 339–353.

[17] Tan Y, Shao R, Li J, Huang H, Wang Y, Zhang M, et al. PITPNC1 fuels radioresistance of rectal cancer by inhibiting reactive oxygen species production. Annals of Translational Medicine. 2020; 8: 126.

[18] Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discovery. 2022; 12: 31–46.

[19] Mehlich D, Marusiak AA. Kinase inhibitors for precision therapy of triple-negative breast cancer: progress, challenges, and new perspectives on targeting this heterogeneous disease. Cancer Letters. 2022; 547: 215775.

[20] Cai YM, Lu ZQ, Li B, Huang JY, Zhang M, Chen C, et al. Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers. Military Medical Research. 2024; 11: 36.

[21] Liu SS, Wan QS, Lv C, Wang JK, Jiang S, Cai D, et al. Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer. BMC Cancer. 2024; 24: 465.

[22] Yin W, Chen G, Li Y, Li R, Jia Z, Zhong C, et al. Identification of a 9-gene signature to enhance biochemical recurrence prediction in primary prostate cancer: a benchmarking study using ten machine learning methods and twelve patient cohorts. Cancer Letters. 2024; 588: 216739.

[23] Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, et al. ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data. The Innovation. 2021; 2: 100141.

[24] Zhong C, Long Z, Yang T, Wang S, Zhong W, Hu F, et al. M6A-modified circRBM33 promotes prostate cancer progression via PDHA1-mediated mitochondrial respiration regulation and presents a potential target for ARSI therapy. International Journal of Biological Sciences. 2023; 19: 1543–1563.

[25] Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Research. 2018; 28: 1747–1756.

[26] Liu Z, Liu L, Weng S, Xu J, Xing Z, Ren Y, et al. BEST: a web application for comprehensive biomarker exploration on large-scale data in solid tumors. Journal of Big Data. 2023; 10: 165.

[27] Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, et al. The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006; 313: 1929–1935.

[28] Shen W, Song Z, Zhong X, Huang M, Shen D, Gao P, et al. Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta. 2022; 1: e36.

[29] Bokhorst LP, Valdagni R, Rannikko A, Kakehi Y, Pickles T, Bangma CH, et al. A decade of active surveillance in the PRIAS study: an update and evaluation of the criteria used to recommend a switch to active treatment. European Urology. 2016; 70: 954–960.

[30] Godtman RA, Holmberg E, Khatami A, Pihl CG, Stranne J, Hugosson J. Long-term results of active surveillance in the göteborg randomized, population-based prostate cancer screening trial. European Urology. 2016; 70: 760–766.

[31] Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. Journal of Clinical Oncology. 2015; 33: 272–277.

[32] Boorjian SA, Thompson RH, Tollefson MK, Rangel LJ, Bergstralh EJ, Blute ML, et al. Long-term risk of clinical progression after biochemical recurrence following radical prostatectomy: the impact of time from surgery to recurrence. European Urology. 2011; 59: 893–899.

[33] Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. Journal of Urology. 2003; 169: 517–523.

[34] Johansson E, Steineck G, Holmberg L, Johansson JE, Nyberg T, Ruutu M, et al. Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the scandinavian prostate cancer group-4 randomised trial. The Lancet Oncology. 2011; 12: 891–899.

[35] Erim DO, Bennett AV, Gaynes BN, Basak RS, Usinger D, Chen RC. Associations between prostate cancer-related anxiety and health-related quality of life. Cancer Medicine. 2020; 9: 4467–4473.

[36] Tan Y, Lin K, Zhao Y, Wu Q, Chen D, Wang J, et al. Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming. Theranostics. 2018; 8: 5452–5468.

[37] Liang J, Liao L, Xie L, Tang W, Yu X, Lu Y, et al. PITPNC1 suppress CD8+ T cell immune function and promote radioresistance in rectal cancer by modulating FASN/CD155. Journal of Translational Medicine. 2024; 22: 117.

[38] Kastenhuber ER, Lowe SW. Putting p53 in context. Cell. 2017; 170: 1062–1078.

[39] Maxwell KN, Cheng HH, Powers J, Gulati R, Ledet EM, Morrison C, et al. Inherited TP53 variants and risk of prostate cancer. European Urology. 2022; 81: 243–250.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)

Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.

Scopus: CiteScore 0.9 (2023) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (https://kanalregister.hkdir.no/publiseringskanaler/Forside).

Submission Turnaround Time

Conferences

Top