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Tumor and adjacent normal tissues were biopsied at the beginning, during, and end of surgery in breast cancer (81) and head/neck squamous cancers (10). mRNA-Seq and microarray profiling revealed significant deregulation across seven hallmarks, validated in independent breast samples. Comparisons with TCGA further supported concordant deregulated genes across cancers.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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biological effects of surgery are examined in this study?","Question",{"text":63,"@type":64},"The study focuses on hypoxia and mechanical stress from surgical removal, which drive rapid gene-expression changes in tumor tissue and the surrounding microenvironment.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were tissue samples collected across the surgery timeline?",{"text":68,"@type":64},"Tumor and adjacent normal tissues were biopsied at three time points: beginning, during, and end of surgery.",{"name":70,"@type":61,"acceptedAnswer":71},"Which cancer hallmarks were found to be significantly deregulated?",{"text":72,"@type":64},"Pathways linked to seven hallmarks were significantly deregulated during resection, including tumor-promoting inflammation, invasion/migration, sustained proliferative signaling, evasion of growth suppressors, altered energetics, angiogenesis, and immune 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Surrounding Microenvironment  \nRohan Chaubal1,2,3, Nilesh Gardi2,3,4, Shalaka Joshi1,2,3, Gouri Pantvaidya1,3, Rasika Kadam3,4, Vaibhav Vanmali3,5, Rohini Hawaldar3,5, Elizabeth Talker2,4, Jaya Chitra1,2, Poonam Gera6, Dimple Bhatia2, Prajakta Kalkar2, Mamta Gurav3,7, Omshree Shetty3,7, Sangeeta Desai3,7, Neeraja M. Krishnan8,  \nNita Nair1,2,3, Vani Parmar1,3,9, Amit Dutt3,10, Binay Panda8, Sudeep Gupta2,3,4, and Rajendra Badwe1,2,3  \nABSTRACT  \n◥  \nSurgery exposes tumor tissue to severe hypoxia and mechanical stress leading to rapid gene expression changes in the tumor and its microenvironment, which remain poorly characterized. We biopsied tumor and adjacent normal tissues from patients with breast (n ¼ 81) and head/neck squamous cancers (HNSC; n ¼ 10) at the beginning (A), during (B), and end of surgery (C) . Tumor/normal RNA from 46/81 patients with breast cancer was subjected to mRNA-Seq using Illumina short-read technology, and from nine patients with HNSC to whole-transcriptome microarray with Illumina BeadArray. Pathways and genes involved in 7 of 10 known cancer hallmarks, namely, tumorpromoting inflammation ( TNF-A, NFK-B, IL18 pathways), activation of invasion and migration (various extracellular matrix– related pathways, cell migration), sustained proliferative signaling (K-Ras Signaling), evasion of growth suppressors (P53 signaling, regulation of cell death), deregulating cellular energetics (response  \nto lipid, secreted factors, and adipogenesis), inducing angiogenesis (hypoxia signaling, myogenesis), and avoiding immune destruction (CTLA4 and PDL1) were significantly deregulated during surgical resection (time points A vs. B vs. C) . These findings were validated using NanoString assays in independent pre/intra/post-operative breast cancer samples from 48 patients. In a comparison of gene expression data from biopsy (analogous to time point A) with surgical resection samples (analogous to time point C) from The Cancer Genome Atlas study, the top deregulated genes were the same as identified in our analysis, in five of the seven studied cancer types. This study suggests that surgical extirpation deregulates the hallmarks of cancer in primary tumors and adjacent normal tissue across different cancers.  \nImplications: Surgery deregulates hallmarks of cancer in human tissue.  \nIntroduction  \nSurgery remains the mainstay of cancer management with curative intent (1) . However, there is also some evidence that there could be metastatic dissemination of cancer cells during surgical removal  \n1Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. 2Hypoxia and Clinical Genomics Lab (Clinician Scientist Laboratory), Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India. 3Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, Maharashtra, India. 4Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. 5Clinical Research Secretariat, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. 6Biorepository, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India. 7Department of Pathology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. 8School of Biotechnology, Jawaharlal Nehru University, New Delhi, India. 93D Printing Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India. 10Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India.  \nCorresponding Authors: Rajendra Badwe, Tata Memorial Hospital, Dr. E. Borges Road, Mumbai, Maharashtra, 400012, India. E-mail: [badwera@tmc.gov.in](badwera@tmc.gov.in); and Sudeep Gupta, [sud","cbCait4meyrzF6GS","https://ap.wps.com/l/cbCait4meyrzF6GS","pdf",14552824,13,"English","# Abstract\n## Introduction\n## Study rationale and experimental design","[{\"question\":\"What biological effects of surgery are examined in this study?\",\"answer\":\"The study focuses on hypoxia and mechanical stress from surgical removal, which drive rapid gene-expression changes in tumor tissue and the surrounding microenvironment.\"},{\"question\":\"How were tissue samples collected across the surgery timeline?\",\"answer\":\"Tumor and adjacent normal tissues were biopsied at three time points: beginning, during, and end of surgery.\"},{\"question\":\"Which cancer hallmarks were found to be significantly deregulated?\",\"answer\":\"Pathways linked to seven hallmarks were significantly deregulated during resection, including tumor-promoting inflammation, invasion/migration, sustained proliferative signaling, evasion of growth suppressors, altered energetics, angiogenesis, and immune evasion.\"}]","Surgical Tumor Resection Deregulates Hallmarks of Cancer in Resected Tissue and the Surrounding Microenvironment | PDF",1789996904,33]